Search

Your search keyword '"Tseng, Alan"' showing total 178 results
Start Over Author "Tseng, Alan"
178 results on '"Tseng, Alan"'

1. Early Administration of Intravenous Hydration and Opioid Analgesics Is Correlated with Decreased Admission Rates during Vaso-Occlusive Episodes in Sickle Cell Disease

Author

Joung, Bowon, primary, Miles, Ethan, additional, Al-Manaseer, Farris, additional, Jeon, Won Jin, additional, Wijaya, Darren, additional, Moon, Jin Hyun, additional, Han, Philip, additional, Lee, Jae, additional, Mehta, Akhil, additional, Tseng, Alan, additional, Ngo, Kaylin, additional, Cao, Huynh, additional, and Chong, Esther G., additional

Published
2024
Full Text
View/download PDF

2. ABO blood group and rhesus factor association with inpatient COVID-19 mortality and severity: a two-year retrospective review

Author

Phan, Alexander T., primary, Ucar, Ari A., additional, Malkoc, Aldin, additional, Hu, Janie, additional, Buxton, Luke, additional, Tseng, Alan W., additional, Dong, Fanglong, additional, Nguyễn, Julie P.T., additional, Modi, Arnav P., additional, Deshpande, Ojas, additional, Lay, Johnson, additional, Ku, Andrew, additional, Ogunyemi, Dotun, additional, and Arabian, Sarkis, additional

Published
2023
Full Text
View/download PDF

3. The impact of impaired insulin regulation on severity of SARS-CoV-2 infection: a 2-year retrospective single-center analysis

Author

Phan, Alexander T., primary, Ucar, Ari, additional, Malkoc, Aldin, additional, Nagori, Essam, additional, Qadir, Aftab, additional, Khosravi, Chayanne, additional, Tseng, Alan, additional, Nguyễ˜ên, Julie P. T., additional, Modi, Arnav P., additional, Deshpande, Ojas, additional, Lay, Johnson, additional, Ku, Andrew, additional, Dong, Fanglong, additional, Ogunyemi, Dotun, additional, and Arabian, Sarkis, additional

Published
2023
Full Text
View/download PDF

5. Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to DNA Damage Independent of TET2

Author

Inoue, Satoshi, Li, Wanda Y., Tseng, Alan, Beerman, Isabel, Elia, Andrew J., Bendall, Sean C., Lemonnier, François, Kron, Ken J., Cescon, David W., Hao, Zhenyue, Lind, Evan F., Takayama, Naoya, Planello, Aline C., Shen, Shu Yi, Shih, Alan H., Larsen, Dana M., Li, Qinxi, Snow, Bryan E., Wakeham, Andrew, Haight, Jillian, Gorrini, Chiara, Bassi, Christian, Thu, Kelsie L., Murakami, Kiichi, Elford, Alisha R., Ueda, Takeshi, Straley, Kimberly, Yen, Katharine E., Melino, Gerry, Cimmino, Luisa, Aifantis, Iannis, Levine, Ross L., De Carvalho, Daniel D., Lupien, Mathieu, Rossi, Derrick J., Nolan, Garry P., Cairns, Rob A., and Mak, Tak W.

Published
2016
Full Text
View/download PDF

10. Autonomic Dysfunction in the Setting of CADASIL Syndrome

Author

Allen, Ricci, Kostick, Nathan, Tseng, Alan, Sirotkin, Igor, and Baldinger, Esther

Subjects
cardiovascular diseases, Case In Point
Abstract

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) syndrome is the most common monogenic inherited cause of stroke. CASE PRESENTATION: A female patient aged > 50 years with genetically proven CADASIL syndrome and an extensive stroke/transient ischemic attack (TIA) history experienced a bradycardic episode following hospitalization for new strokelike symptoms. The literature of cardiac involvement in CADASIL syndrome is limited, with no definitive recommendations for surveillance and screening. CONCLUSIONS: This case report postulates that cardiac surveillance and screening may be indicated for patients with CADASIL syndrome.

Published
2022

18. regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction

Author

Inuzuka, Hiroyuki, Shaik, Shavali, Onoyama, Ichiro, Gao, Daming, Tseng, Alan, Maser, Richard S., Zhai, Bo, Wan, Lixin, Gutierrez, Alejandro, Lau, Alan W., Xiao, Yonghong, Christie, Amanda L., Aster, Jon, Settleman, Jeffrey, Gygi, Steven P., Kung, Andrew L., Look, Thomas, Nakayama, Keiichi I., DePinho, Ronald A., and Wei, Wenyi

Subjects
Ubiquitin -- Genetic aspects, Proteins -- Genetic aspects, Apoptosis -- Management -- Genetic aspects, Company business management, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The effective use of targeted therapy is highly dependent on the identification of responder patient populations. Loss of FBW7, which encodes a tumour-suppressor protein, is frequently found in various types of human cancer, including breast cancer, colon cancer (1) and T-cell acute lymphoblastic leukaemia (T-ALL) (2). In line with these genomic data, engineered deletion of Fbw7 in mouse T cells results in T-ALL (3-5), validating FBW7 as a T-ALL tumour suppressor. Determining the precise molecular mechanisms by which FBW7 exerts antitumour activity is an area of intensive investigation. These mechanisms are thought to relate in part to FBW7-mediated destruction of key proteins relevant to cancer, including Jun (6), Myc (7), cyclin E (8) and notch 1 (ref. 9), all of which have oncoprotein activity and are overexpressed in various human cancers, including leukaemia. In addition to accelerating cell growth (10), overexpression of Jun, Myc or notch 1 can also induce programmed cell death (11). Thus, considerable uncertainty surrounds how FBW7-deficient cells evade cell death in the setting of upregulated Jun, Mbc and/or notch 1. Here we show that the E3 ubiquitin ligase [SCF.sup.FBW7] (a SKP1-cullin-1-F-box complex that contains FBW7 as the F-box protein) governs cellular apoptosis by targeting MCL1, a pro-survival BCL2 family member, for ubiquitylation and destruction in a manner that depends on phosphorylation by glycogen synthase kinase 3. Human T-ALL cell lines showed a close relationship between FBW7 loss and MCL1 overexpression. Correspondingly, T-ALL cell lines with defective FBW7 are particularly sensitive to the multi-kinase inhibitor sorafenib but resistant to the BCL2 antagonist ABT-737. On the genetic level, FBW7 reconstitution or MCL1 depletion restores sensitivity to ABT-737, establishing MCL1 as a therapeutically relevant bypass survival mechanism that enables FBW7-deficient cells to evade apoptosis. Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7-deficient T-ALL., MCL1 is frequently overexpressed in various leukaemias through mechanisms that are not fully understood (12). MCL1 is distinct from other BCL2 family members in its extremely unstable nature (13), which [...]

Published
2011
Full Text
View/download PDF

21. MPO Negatively Regulates Neutrophil-EC Interactions By Impairing ��M��2 Integrin in Sterile Inflammation

Author

Tseng, Alan

Subjects
Uncategorized
Abstract

Interactions between neutrophils with platelets and endothelial cells (ECs) contribute to vascular occlusion and tissue damage in sterile inflammatory conditions. However, the molecular mechanisms underlying the cell-cell interactions are not fully understood. Previous studies show that reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), modulate neutrophil ��M��2 integrin function and play a role in mediating platelet-neutrophil heterotypic interactions. In this study, we further characterize a role for myeloperoxidase (MPO) in regulating neutrophil adhesive function through ��M��2 integrin. Using real-time fluorescence intravital microscopy and in vitro assays, we found that loss of MPO enhanced neutrophil-EC interactions and subsequent neutrophil transmigration under inflammatory conditions but did not affect neutrophil-platelet interactions. Using both genetic and pharmacologic approaches, we showed that following activation, MPO KO neutrophils had enhanced extracellular H2O2 production and increased surface level of ��M��2 integrin and that these effects were dependent on MPO activity. Our in vivo studies using a hepatic ischemia/reperfusion-induced inflammation model found that compared to WT mice, neutrophils from MPO KO mice had a pro-migratory phenotype while tissue damage was reduced. These results indicate that under sterile inflammatory conditions, MPO plays a negative role in the adhesive and migratory function of neutrophils by diminishing ��M��2 integrin function.

Published
2021
Full Text
View/download PDF

26. Akt finds its new path to regulate cell cycle through modulating Skp2 activity and its destruction by APC/Cdh1

Author

Tseng Alan, Inuzuka Hiroyuki, Gao Daming, and Wei Wenyi

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Abstract Skp2 over-expression has been observed in many human cancers. However, the mechanisms underlying elevated Skp2 expression have remained elusive. We recently reported that Akt1, but not Akt2, directly controls Skp2 stability by interfering with its association with APC/Cdh1. As a result, Skp2 degradation is protected in cancer cells with elevated Akt activity. This finding expands our knowledge of how specific kinase cascades influence proteolysis governed by APC/Cdh1 complexes. However, it awaits further investigation to elucidate whether the PI3K/Akt circuit affects other APC/Cdh1 substrates. Our results further strengthen the argument that different Akt isoforms might have distinct, even opposing functions in the regulation of cell growth or migration. In addition, we noticed that Ser72 is localized in a putative Nuclear Localization Sequence (NLS), and that phosphorylation of Ser72 disrupts the NLS and thus promotes Skp2 cytoplasmic translocation. This finding links elevated Akt activity with the observed cytoplasmic Skp2 staining in aggressive breast and prostate cancer patients. Furthermore, it provides the rationale for the development of specific Akt1 inhibitors as efficient anti-cancer therapeutic agents.

Published
2009
Full Text
View/download PDF

31. IDH1mutation contributes to myeloid dysplasia in mice by disturbing heme biosynthesis and erythropoiesis

Author

Gu, Yu, Yang, Risheng, Yang, Ying, Zhao, Yuanlin, Wakeham, Andrew, Li, Wanda Y., Tseng, Alan, Leca, Julie, Berger, Thorsten, Saunders, Mary, Fortin, Jerome, Gao, Xing, Yuan, Yuan, Xiao, Liming, Zhang, Feng, Zhang, Lijun, Gao, Guangxun, Zhou, Wenjing, Wang, Zhe, Mak, Tak W., and Ye, Jing

Abstract

Isocitrate dehydrogenase (IDH) mutations are common genetic alterations in myeloid disorders, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Epigenetic changes, including abnormal histone and DNA methylation, have been implicated in the pathogenic build-up of hematopoietic progenitors, but it is still unclear whether and how IDHmutations themselves affect hematopoiesis. Here, we show that IDH1-mutant mice develop myeloid dysplasia in that these animals exhibit anemia, ineffective erythropoiesis, and increased immature progenitors and erythroblasts. In erythroid cells of these mice, D-2-hydroxyglutarate, an aberrant metabolite produced by the mutant IDH1enzyme, inhibits oxoglutarate dehydrogenase activity and diminishes succinyl–coenzyme A (CoA) production. This succinyl-CoA deficiency attenuates heme biosynthesis in IDH1-mutant hematopoietic cells, thus blocking erythroid differentiation at the late erythroblast stage and the erythroid commitment of hematopoietic stem cells, while the exogenous succinyl-CoA or 5-ALA rescues erythropoiesis in IDH1-mutant erythroid cells. Heme deficiency also impairs heme oxygenase-1 expression, which reduces levels of important heme catabolites such as biliverdin and bilirubin. These deficits result in accumulation of excessive reactive oxygen species that induce the cell death of IDH1-mutant erythroid cells. Our results clearly show the essential role of IDH1in normal erythropoiesis and describe how its mutation leads to myeloid disorders. These data thus have important implications for the devising of new treatments for IDH-mutant tumors.

Published
2021
Full Text
View/download PDF

32. Specific Inhibition of AKT with ARQ 092, an Orally-Available Selective AKT Inhibitor, Attenuates Acute Vaso-Occlusive Events in Sickle Cell Disease

Author

Li, Jing, primary, Kim, Kyungho, additional, Tseng, Alan, additional, Barazia, Andrew, additional, Youn, Seock-Won, additional, Abbadessa, Giovanni, additional, Yu, Yi, additional, Schwartz, Brian, additional, Andrews, Robert K, additional, Gordeuk, Victor R., additional, and Cho, Jaehyung, additional

Published
2016
Full Text
View/download PDF

35. Ear-Shaped Stable Auricular Cartilage Engineered from Extensively Expanded Chondrocytes in an Immunocompetent Experimental Animal Model

Author

Pomerantseva, Irina, primary, Bichara, David A., additional, Tseng, Alan, additional, Cronce, Michael J., additional, Cervantes, Thomas M., additional, Kimura, Anya M., additional, Neville, Craig M., additional, Roscioli, Nick, additional, Vacanti, Joseph P., additional, Randolph, Mark A., additional, and Sundback, Cathryn A., additional

Published
2016
Full Text
View/download PDF

41. Drosophila Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

Author

Leung, Wilson, primary, Shaffer, Christopher D, additional, Reed, Laura K, additional, Smith, Sheryl T, additional, Barshop, William, additional, Dirkes, William, additional, Dothager, Matthew, additional, Lee, Paul, additional, Wong, Jeannette, additional, Xiong, David, additional, Yuan, Han, additional, Bedard, James E J, additional, Machone, Joshua F, additional, Patterson, Seantay D, additional, Price, Amber L, additional, Turner, Bryce A, additional, Robic, Srebrenka, additional, Luippold, Erin K, additional, McCartha, Shannon R, additional, Walji, Tezin A, additional, Walker, Chelsea A, additional, Saville, Kenneth, additional, Abrams, Marita K, additional, Armstrong, Andrew R, additional, Armstrong, William, additional, Bailey, Robert J, additional, Barberi, Chelsea R, additional, Beck, Lauren R, additional, Blaker, Amanda L, additional, Blunden, Christopher E, additional, Brand, Jordan P, additional, Brock, Ethan J, additional, Brooks, Dana W, additional, Brown, Marie, additional, Butzler, Sarah C, additional, Clark, Eric M, additional, Clark, Nicole B, additional, Collins, Ashley A, additional, Cotteleer, Rebecca J, additional, Cullimore, Peterson R, additional, Dawson, Seth G, additional, Docking, Carter T, additional, Dorsett, Sasha L, additional, Dougherty, Grace A, additional, Downey, Kaitlyn A, additional, Drake, Andrew P, additional, Earl, Erica K, additional, Floyd, Trevor G, additional, Forsyth, Joshua D, additional, Foust, Jonathan D, additional, Franchi, Spencer L, additional, Geary, James F, additional, Hanson, Cynthia K, additional, Harding, Taylor S, additional, Harris, Cameron B, additional, Heckman, Jonathan M, additional, Holderness, Heather L, additional, Howey, Nicole A, additional, Jacobs, Dontae A, additional, Jewell, Elizabeth S, additional, Kaisler, Maria, additional, Karaska, Elizabeth A, additional, Kehoe, James L, additional, Koaches, Hannah C, additional, Koehler, Jessica, additional, Koenig, Dana, additional, Kujawski, Alexander J, additional, Kus, Jordan E, additional, Lammers, Jennifer A, additional, Leads, Rachel R, additional, Leatherman, Emily C, additional, Lippert, Rachel N, additional, Messenger, Gregory S, additional, Morrow, Adam T, additional, Newcomb, Victoria, additional, Plasman, Haley J, additional, Potocny, Stephanie J, additional, Powers, Michelle K, additional, Reem, Rachel M, additional, Rennhack, Jonathan P, additional, Reynolds, Katherine R, additional, Reynolds, Lyndsey A, additional, Rhee, Dong K, additional, Rivard, Allyson B, additional, Ronk, Adam J, additional, Rooney, Meghan B, additional, Rubin, Lainey S, additional, Salbert, Luke R, additional, Saluja, Rasleen K, additional, Schauder, Taylor, additional, Schneiter, Allison R, additional, Schulz, Robert W, additional, Smith, Karl E, additional, Spencer, Sarah, additional, Swanson, Bryant R, additional, Tache, Melissa A, additional, Tewilliager, Ashley A, additional, Tilot, Amanda K, additional, VanEck, Eve, additional, Villerot, Matthew M, additional, Vylonis, Megan B, additional, Watson, David T, additional, Wurzler, Juliana A, additional, Wysocki, Lauren M, additional, Yalamanchili, Monica, additional, Zaborowicz, Matthew A, additional, Emerson, Julia A, additional, Ortiz, Carlos, additional, Deuschle, Frederic J, additional, DiLorenzo, Lauren A, additional, Goeller, Katie L, additional, Macchi, Christopher R, additional, Muller, Sarah E, additional, Pasierb, Brittany D, additional, Sable, Joseph E, additional, Tucci, Jessica M, additional, Tynon, Marykathryn, additional, Dunbar, David A, additional, Beken, Levent H, additional, Conturso, Alaina C, additional, Danner, Benjamin L, additional, DeMichele, Gabriella A, additional, Gonzales, Justin A, additional, Hammond, Maureen S, additional, Kelley, Colleen V, additional, Kelly, Elisabeth A, additional, Kulich, Danielle, additional, Mageeney, Catherine M, additional, McCabe, Nikie L, additional, Newman, Alyssa M, additional, Spaeder, Lindsay A, additional, Tumminello, Richard A, additional, Revie, Dennis, additional, Benson, Jonathon M, additional, Cristostomo, Michael C, additional, DaSilva, Paolo A, additional, Harker, Katherine S, additional, Jarrell, Jenifer N, additional, Jimenez, Luis A, additional, Katz, Brandon M, additional, Kennedy, William R, additional, Kolibas, Kimberly S, additional, LeBlanc, Mark T, additional, Nguyen, Trung T, additional, Nicolas, Daniel S, additional, Patao, Melissa D, additional, Patao, Shane M, additional, Rupley, Bryan J, additional, Sessions, Bridget J, additional, Weaver, Jennifer A, additional, Goodman, Anya L, additional, Alvendia, Erica L, additional, Baldassari, Shana M, additional, Brown, Ashley S, additional, Chase, Ian O, additional, Chen, Maida, additional, Chiang, Scott, additional, Cromwell, Avery B, additional, Custer, Ashley F, additional, DiTommaso, Tia M, additional, El-Adaimi, Jad, additional, Goscinski, Nora C, additional, Grove, Ryan A, additional, Gutierrez, Nestor, additional, Harnoto, Raechel S, additional, Hedeen, Heather, additional, Hong, Emily L, additional, Hopkins, Barbara L, additional, Huerta, Vilma F, additional, Khoshabian, Colin, additional, LaForge, Kristin M, additional, Lee, Cassidy T, additional, Lewis, Benjamin M, additional, Lydon, Anniken M, additional, Maniaci, Brian J, additional, Mitchell, Ryan D, additional, Morlock, Elaine V, additional, Morris, William M, additional, Naik, Priyanka, additional, Olson, Nicole C, additional, Osterloh, Jeannette M, additional, Perez, Marcos A, additional, Presley, Jonathan D, additional, Randazzo, Matt J, additional, Regan, Melanie K, additional, Rossi, Franca G, additional, Smith, Melanie A, additional, Soliterman, Eugenia A, additional, Sparks, Ciani J, additional, Tran, Danny L, additional, Wan, Tiffany, additional, Welker, Anne A, additional, Wong, Jeremy N, additional, Sreenivasan, Aparna, additional, Youngblom, Jim, additional, Adams, Andrew, additional, Alldredge, Justin, additional, Bryant, Ashley, additional, Carranza, David, additional, Cifelli, Alyssa, additional, Coulson, Kevin, additional, Debow, Calise, additional, Delacruz, Noelle, additional, Emerson, Charlene, additional, Farrar, Cassandra, additional, Foret, Don, additional, Garibay, Edgar, additional, Gooch, John, additional, Heslop, Michelle, additional, Kaur, Sukhjit, additional, Khan, Ambreen, additional, Kim, Van, additional, Lamb, Travis, additional, Lindbeck, Peter, additional, Lucas, Gabi, additional, Macias, Elizabeth, additional, Martiniuc, Daniela, additional, Mayorga, Lissett, additional, Medina, Joseph, additional, Membreno, Nelson, additional, Messiah, Shady, additional, Neufeld, Lacey, additional, Nguyen, San Francisco, additional, Nichols, Zachary, additional, Odisho, George, additional, Peterson, Daymon, additional, Rodela, Laura, additional, Rodriguez, Priscilla, additional, Rodriguez, Vanessa, additional, Ruiz, Jorge, additional, Sherrill, Will, additional, Silva, Valeria, additional, Sparks, Jeri, additional, Statton, Geeta, additional, Townsend, Ashley, additional, Valdez, Isabel, additional, Waters, Mary, additional, Westphal, Kyle, additional, Winkler, Stacey, additional, Zumkehr, Joannee, additional, DeJong, Randall J, additional, Hoogewerf, Arlene J, additional, Ackerman, Cheri M, additional, Armistead, Isaac O, additional, Baatenburg, Lara, additional, Borr, Matthew J, additional, Brouwer, Lindsay K, additional, Burkhart, Brandon J, additional, Bushhouse, Kelsey T, additional, Cesko, Lejla, additional, Choi, Tiffany Y Y, additional, Cohen, Heather, additional, Damsteegt, Amanda M, additional, Darusz, Jess M, additional, Dauphin, Cory M, additional, Davis, Yelena P, additional, Diekema, Emily J, additional, Drewry, Melissa, additional, Eisen, Michelle E M, additional, Faber, Hayley M, additional, Faber, Katherine J, additional, Feenstra, Elizabeth, additional, Felzer-Kim, Isabella T, additional, Hammond, Brandy L, additional, Hendriksma, Jesse, additional, Herrold, Milton R, additional, Hilbrands, Julia A, additional, Howell, Emily J, additional, Jelgerhuis, Sarah A, additional, Jelsema, Timothy R, additional, Johnson, Benjamin K, additional, Jones, Kelly K, additional, Kim, Anna, additional, Kooienga, Ross D, additional, Menyes, Erika E, additional, Nollet, Eric A, additional, Plescher, Brittany E, additional, Rios, Lindsay, additional, Rose, Jenny L, additional, Schepers, Allison J, additional, Scott, Geoff, additional, Smith, Joshua R, additional, Sterling, Allison M, additional, Tenney, Jenna C, additional, Uitvlugt, Chris, additional, VanDyken, Rachel E, additional, VanderVennen, Marielle, additional, Vue, Samantha, additional, Kokan, Nighat P, additional, Agbley, Kwabea, additional, Boham, Sampson K, additional, Broomfield, Daniel, additional, Chapman, Kayla, additional, Dobbe, Ali, additional, Dobbe, Ian, additional, Harrington, William, additional, Ibrahem, Marwan, additional, Kennedy, Andre, additional, Koplinsky, Chad A, additional, Kubricky, Cassandra, additional, Ladzekpo, Danielle, additional, Pattison, Claire, additional, Ramirez, Roman E, additional, Wande, Lucia, additional, Woehlke, Sarah, additional, Wawersik, Matthew, additional, Kiernan, Elizabeth, additional, Thompson, Jeffrey S, additional, Banker, Roxanne, additional, Bartling, Justina R, additional, Bhatiya, Chinmoy I, additional, Boudoures, Anna L, additional, Christiansen, Lena, additional, Fosselman, Daniel S, additional, French, Kristin M, additional, Gill, Ishwar S, additional, Havill, Jessen T, additional, Johnson, Jaelyn L, additional, Keny, Lauren J, additional, Kerber, John M, additional, Klett, Bethany M, additional, Kufel, Christina N, additional, May, Francis J, additional, Mecoli, Jonathan P, additional, Merry, Callie R, additional, Meyer, Lauren R, additional, Miller, Emily G, additional, Mullen, Gregory J, additional, Palozola, Katherine C, additional, Pfeil, Jacob J, additional, Thomas, Jessica G, additional, Verbofsky, Evan M, additional, Spana, Eric P, additional, Agarwalla, Anant, additional, Chapman, Julia, additional, Chlebina, Ben, additional, Chong, Insun, additional, Falk, I N, additional, Fitzgibbons, John D, additional, Friedman, Harrison, additional, Ighile, Osagie, additional, Kim, Andrew J, additional, Knouse, Kristin A, additional, Kung, Faith, additional, Mammo, Danny, additional, Ng, Chun Leung, additional, Nikam, Vinayak S, additional, Norton, Diana, additional, Pham, Philip, additional, Polk, Jessica W, additional, Prasad, Shreya, additional, Rankin, Helen, additional, Ratliff, Camille D, additional, Scala, Victoria, additional, Schwartz, Nicholas U, additional, Shuen, Jessica A, additional, Xu, Amy, additional, Xu, Thomas Q, additional, Zhang, Yi, additional, Rosenwald, Anne G, additional, Burg, Martin G, additional, Adams, Stephanie J, additional, Baker, Morgan, additional, Botsford, Bobbi, additional, Brinkley, Briana, additional, Brown, Carter, additional, Emiah, Shadie, additional, Enoch, Erica, additional, Gier, Chad, additional, Greenwell, Alyson, additional, Hoogenboom, Lindsay, additional, Matthews, Jordan E, additional, McDonald, Mitchell, additional, Mercer, Amanda, additional, Monsma, Nicholaus, additional, Ostby, Kristine, additional, Ramic, Alen, additional, Shallman, Devon, additional, Simon, Matthew, additional, Spencer, Eric, additional, Tomkins, Trisha, additional, Wendland, Pete, additional, Wylie, Anna, additional, Wolyniak, Michael J, additional, Robertson, Gregory M, additional, Smith, Samuel I, additional, DiAngelo, Justin R, additional, Sassu, Eric D, additional, Bhalla, Satish C, additional, Sharif, Karim A, additional, Choeying, Tenzin, additional, Macias, Jason S, additional, Sanusi, Fareed, additional, Torchon, Karvyn, additional, Bednarski, April E, additional, Alvarez, Consuelo J, additional, Davis, Kristen C, additional, Dunham, Carrie A, additional, Grantham, Alaina J, additional, Hare, Amber N, additional, Schottler, Jennifer, additional, Scott, Zackary W, additional, Kuleck, Gary A, additional, Yu, Nicole S, additional, Kaehler, Marian M, additional, Jipp, Jacob, additional, Overvoorde, Paul J, additional, Shoop, Elizabeth, additional, Cyrankowski, Olivia, additional, Hoover, Betsy, additional, Kusner, Matt, additional, Lin, Devry, additional, Martinov, Tijana, additional, Misch, Jonathan, additional, Salzman, Garrett, additional, Schiedermayer, Holly, additional, Snavely, Michael, additional, Zarrasola, Stephanie, additional, Parrish, Susan, additional, Baker, Atlee, additional, Beckett, Alissa, additional, Belella, Carissa, additional, Bryant, Julie, additional, Conrad, Turner, additional, Fearnow, Adam, additional, Gomez, Carolina, additional, Herbstsomer, Robert A, additional, Hirsch, Sarah, additional, Johnson, Christen, additional, Jones, Melissa, additional, Kabaso, Rita, additional, Lemmon, Eric, additional, Vieira, Carolina Marques dos Santos, additional, McFarland, Darryl, additional, McLaughlin, Christopher, additional, Morgan, Abbie, additional, Musokotwane, Sepo, additional, Neutzling, William, additional, Nietmann, Jana, additional, Paluskievicz, Christina, additional, Penn, Jessica, additional, Peoples, Emily, additional, Pozmanter, Caitlin, additional, Reed, Emily, additional, Rigby, Nichole, additional, Schmidt, Lasse, additional, Shelton, Micah, additional, Shuford, Rebecca, additional, Tirasawasdichai, Tiara, additional, Undem, Blair, additional, Urick, Damian, additional, Vondy, Kayla, additional, Yarrington, Bryan, additional, Eckdahl, Todd T, additional, Poet, Jeffrey L, additional, Allen, Alica B, additional, Anderson, John E, additional, Barnett, Jason M, additional, Baumgardner, Jordan S, additional, Brown, Adam D, additional, Carney, Jordan E, additional, Chavez, Ramiro A, additional, Christgen, Shelbi L, additional, Christie, Jordan S, additional, Clary, Andrea N, additional, Conn, Michel A, additional, Cooper, Kristen M, additional, Crowley, Matt J, additional, Crowley, Samuel T, additional, Doty, Jennifer S, additional, Dow, Brian A, additional, Edwards, Curtis R, additional, Elder, Darcie D, additional, Fanning, John P, additional, Janssen, Bridget M, additional, Lambright, Anthony K, additional, Lane, Curtiss E, additional, Limle, Austin B, additional, Mazur, Tammy, additional, McCracken, Marly R, additional, McDonough, Alexa M, additional, Melton, Amy D, additional, Minnick, Phillip J, additional, Musick, Adam E, additional, Newhart, William H, additional, Noynaert, Joseph W, additional, Ogden, Bradley J, additional, Sandusky, Michael W, additional, Schmuecker, Samantha M, additional, Shipman, Anna L, additional, Smith, Anna L, additional, Thomsen, Kristen M, additional, Unzicker, Matthew R, additional, Vernon, William B, additional, Winn, Wesley W, additional, Woyski, Dustin S, additional, Zhu, Xiao, additional, Du, Chunguang, additional, Ament, Caitlin, additional, Aso, Soham, additional, Bisogno, Laura Simone, additional, Caronna, Jason, additional, Fefelova, Nadezhda, additional, Lopez, Lenin, additional, Malkowitz, Lorraine, additional, Marra, Jonathan, additional, Menillo, Daniella, additional, Obiorah, Ifeanyi, additional, Onsarigo, Eric Nyabeta, additional, Primus, Shekerah, additional, Soos, Mahdi, additional, Tare, Archana, additional, Zidan, Ameer, additional, Jones, Christopher J, additional, Aronhalt, Todd, additional, Bellush, James M, additional, Burke, Christa, additional, DeFazio, Steve, additional, Does, Benjamin R, additional, Johnson, Todd D, additional, Keysock, Nicholas, additional, Knudsen, Nelson H, additional, Messler, James, additional, Myirski, Kevin, additional, Rekai, Jade Lea, additional, Rempe, Ryan Michael, additional, Salgado, Michael S, additional, Stagaard, Erica, additional, Starcher, Justin R, additional, Waggoner, Andrew W, additional, Yemelyanova, Anastasia K, additional, Hark, Amy T, additional, Bertolet, Anne, additional, Kuschner, Cyrus E, additional, Parry, Kesley, additional, Quach, Michael, additional, Shantzer, Lindsey, additional, Shaw, Mary E, additional, Smith, Mary A, additional, Glenn, Omolara, additional, Mason, Portia, additional, Williams, Charlotte, additional, Key, S Catherine Silver, additional, Henry, Tyneshia C P, additional, Johnson, Ashlee G, additional, White, Jackie X, additional, Haberman, Adam, additional, Asinof, Sam, additional, Drumm, Kelly, additional, Freeburg, Trip, additional, Safa, Nadia, additional, Schultz, Darrin, additional, Shevin, Yakov, additional, Svoronos, Petros, additional, Vuong, Tam, additional, Wellinghoff, Jules, additional, Hoopes, Laura L M, additional, Chau, Kim M, additional, Ward, Alyssa, additional, Regisford, E Gloria C, additional, Augustine, LaJerald, additional, Davis-Reyes, Brionna, additional, Echendu, Vivienne, additional, Hales, Jasmine, additional, Ibarra, Sharon, additional, Johnson, Lauriaun, additional, Ovu, Steven, additional, Braverman, John M, additional, Bahr, Thomas J, additional, Caesar, Nicole M, additional, Campana, Christopher, additional, Cassidy, Daniel W, additional, Cognetti, Peter A, additional, English, Johnathan D, additional, Fadus, Matthew C, additional, Fick, Cameron N, additional, Freda, Philip J, additional, Hennessy, Bryan M, additional, Hockenberger, Kelsey, additional, Jones, Jennifer K, additional, King, Jessica E, additional, Knob, Christopher R, additional, Kraftmann, Karen J, additional, Li, Linghui, additional, Lupey, Lena N, additional, Minniti, Carl J, additional, Minton, Thomas F, additional, Moran, Joseph V, additional, Mudumbi, Krishna, additional, Nordman, Elizabeth C, additional, Puetz, William J, additional, Robinson, Lauren M, additional, Rose, Thomas J, additional, Sweeney, Edward P, additional, Timko, Ashley S, additional, Paetkau, Don W, additional, Eisler, Heather L, additional, Aldrup, Megan E, additional, Bodenberg, Jessica M, additional, Cole, Mara G, additional, Deranek, Kelly M, additional, DeShetler, Megan, additional, Dowd, Rose M, additional, Eckardt, Alexandra K, additional, Ehret, Sharon C, additional, Fese, Jessica, additional, Garrett, Amanda D, additional, Kammrath, Anna, additional, Kappes, Michelle L, additional, Light, Morgan R, additional, Meier, Anne C, additional, O’Rouke, Allison, additional, Perella, Mallory, additional, Ramsey, Kimberley, additional, Ramthun, Jennifer R, additional, Reilly, Mary T, additional, Robinett, Deirdre, additional, Rossi, Nadine L, additional, Schueler, Mary Grace, additional, Shoemaker, Emma, additional, Starkey, Kristin M, additional, Vetor, Ashley, additional, Vrable, Abby, additional, Chandrasekaran, Vidya, additional, Beck, Christopher, additional, Hatfield, Kristen R, additional, Herrick, Douglas A, additional, Khoury, Christopher B, additional, Lea, Charlotte, additional, Louie, Christopher A, additional, Lowell, Shannon M, additional, Reynolds, Thomas J, additional, Schibler, Jeanine, additional, Scoma, Alexandra H, additional, Smith-Gee, Maxwell T, additional, Tuberty, Sarah, additional, Smith, Christopher D, additional, Lopilato, Jane E, additional, Hauke, Jeanette, additional, Roecklein-Canfield, Jennifer A, additional, Corrielus, Maureen, additional, Gilman, Hannah, additional, Intriago, Stephanie, additional, Maffa, Amanda, additional, Rauf, Sabya A, additional, Thistle, Katrina, additional, Trieu, Melissa, additional, Winters, Jenifer, additional, Yang, Bib, additional, Hauser, Charles R, additional, Abusheikh, Tariq, additional, Ashrawi, Yara, additional, Benitez, Pedro, additional, Boudreaux, Lauren R, additional, Bourland, Megan, additional, Chavez, Miranda, additional, Cruz, Samantha, additional, Elliott, GiNell, additional, Farek, Jesse R, additional, Flohr, Sarah, additional, Flores, Amanda H, additional, Friedrichs, Chelsey, additional, Fusco, Zach, additional, Goodwin, Zane, additional, Helmreich, Eric, additional, Kiley, John, additional, Knepper, John Mark, additional, Langner, Christine, additional, Martinez, Megan, additional, Mendoza, Carlos, additional, Naik, Monal, additional, Ochoa, Andrea, additional, Ragland, Nicolas, additional, Raimey, England, additional, Rathore, Sunil, additional, Reza, Evangelina, additional, Sadovsky, Griffin, additional, Seydoux, Marie-Isabelle B, additional, Smith, Jonathan E, additional, Unruh, Anna K, additional, Velasquez, Vicente, additional, Wolski, Matthew W, additional, Gosser, Yuying, additional, Govind, Shubha, additional, Clarke-Medley, Nicole, additional, Guadron, Leslie, additional, Lau, Dawn, additional, Lu, Alvin, additional, Mazzeo, Cheryl, additional, Meghdari, Mariam, additional, Ng, Simon, additional, Pamnani, Brad, additional, Plante, Olivia, additional, Shum, Yuki Kwan Wa, additional, Song, Roy, additional, Johnson, Diana E, additional, Abdelnabi, Mai, additional, Archambault, Alexi, additional, Chamma, Norma, additional, Gaur, Shailly, additional, Hammett, Deborah, additional, Kandahari, Adrese, additional, Khayrullina, Guzal, additional, Kumar, Sonali, additional, Lawrence, Samantha, additional, Madden, Nigel, additional, Mandelbaum, Max, additional, Milnthorp, Heather, additional, Mohini, Shiv, additional, Patel, Roshni, additional, Peacock, Sarah J, additional, Perling, Emily, additional, Quintana, Amber, additional, Rahimi, Michael, additional, Ramirez, Kristen, additional, Singhal, Rishi, additional, Weeks, Corinne, additional, Wong, Tiffany, additional, Gillis, Aubree T, additional, Moore, Zachary D, additional, Savell, Christopher D, additional, Watson, Reece, additional, Mel, Stephanie F, additional, Anilkumar, Arjun A, additional, Bilinski, Paul, additional, Castillo, Rostislav, additional, Closser, Michael, additional, Cruz, Nathalia M, additional, Dai, Tiffany, additional, Garbagnati, Giancarlo F, additional, Horton, Lanor S, additional, Kim, Dongyeon, additional, Lau, Joyce H, additional, Liu, James Z, additional, Mach, Sandy D, additional, Phan, Thu A, additional, Ren, Yi, additional, Stapleton, Kenneth E, additional, Strelitz, Jean M, additional, Sunjed, Ray, additional, Stamm, Joyce, additional, Anderson, Morgan C, additional, Bonifield, Bethany Grace, additional, Coomes, Daniel, additional, Dillman, Adam, additional, Durchholz, Elaine J, additional, Fafara-Thompson, Antoinette E, additional, Gross, Meleah J, additional, Gygi, Amber M, additional, Jackson, Lesley E, additional, Johnson, Amy, additional, Kocsisova, Zuzana, additional, Manghelli, Joshua L, additional, McNeil, Kylie, additional, Murillo, Michael, additional, Naylor, Kierstin L, additional, Neely, Jessica, additional, Ogawa, Emmy E, additional, Rich, Ashley, additional, Rogers, Anna, additional, Spencer, J Devin, additional, Stemler, Kristina M, additional, Throm, Allison A, additional, Van Camp, Matt, additional, Weihbrecht, Katie, additional, Wiles, T Aaron, additional, Williams, Mallory A, additional, Williams, Matthew, additional, Zoll, Kyle, additional, Bailey, Cheryl, additional, Zhou, Leming, additional, Balthaser, Darla M, additional, Bashiri, Azita, additional, Bower, Mindy E, additional, Florian, Kayla A, additional, Ghavam, Nazanin, additional, Greiner-Sosanko, Elizabeth S, additional, Karim, Helmet, additional, Mullen, Victor W, additional, Pelchen, Carly E, additional, Yenerall, Paul M, additional, Zhang, Jiayu, additional, Rubin, Michael R, additional, Arias-Mejias, Suzette M, additional, Bermudez-Capo, Armando G, additional, Bernal-Vega, Gabriela V, additional, Colon-Vazquez, Mariela, additional, Flores-Vazquez, Arelys, additional, Gines-Rosario, Mariela, additional, Llavona-Cartagena, Ivan G, additional, Martinez-Rodriguez, Javier O, additional, Ortiz-Fuentes, Lionel, additional, Perez-Colomba, Eliezer O, additional, Perez-Otero, Joseph, additional, Rivera, Elisandra, additional, Rodriguez-Giron, Luke J, additional, Santiago-Sanabria, Arnaldo J, additional, Senquiz-Gonzalez, Andrea M, additional, delValle, Frank R Soto, additional, Vargas-Franco, Dorianmarie, additional, Velázquez-Soto, Karla I, additional, Zambrana-Burgos, Joan D, additional, Martinez-Cruzado, Juan Carlos, additional, Asencio-Zayas, Lillyann, additional, Babilonia-Figueroa, Kevin, additional, Beauchamp-Pérez, Francis D, additional, Belén-Rodríguez, Juliana, additional, Bracero-Quiñones, Luciann, additional, Burgos-Bula, Andrea P, additional, Collado-Méndez, Xavier A, additional, Colón-Cruz, Luis R, additional, Correa-Muller, Ana I, additional, Crooke-Rosado, Jonathan L, additional, Cruz-García, José M, additional, Defendini-Ávila, Marianna, additional, Delgado-Peraza, Francheska M, additional, Feliciano-Cancela, Alex J, additional, Gónzalez-Pérez, Valerie M, additional, Guiblet, Wilfried, additional, Heredia-Negrón, Aldo, additional, Hernández-Muñiz, Jennifer, additional, Irizarry-González, Lourdes N, additional, Laboy-Corales, Ángel L, additional, Llaurador-Caraballo, Gabriela A, additional, Marín-Maldonado, Frances, additional, Marrero-Llerena, Ulises, additional, Martell-Martínez, Héctor A, additional, Martínez-Traverso, Idaliz M, additional, Medina-Ortega, Kiara N, additional, Méndez-Castellanos, Sonya G, additional, Menéndez-Serrano, Krizia C, additional, Morales-Caraballo, Carol I, additional, Ortiz-DeChoudens, Saryleine, additional, Ortiz-Ortiz, Patricia, additional, Pagán-Torres, Hendrick, additional, Pérez-Afanador, Diana, additional, Quintana-Torres, Enid M, additional, Ramírez-Aponte, Edwin G, additional, Riascos-Cuero, Carolina, additional, Rivera-Llovet, Michelle S, additional, Rivera-Pagán, Ingrid T, additional, Rivera-Vicéns, Ramón E, additional, Robles-Juarbe, Fabiola, additional, Rodríguez-Bonilla, Lorraine, additional, Rodríguez-Echevarría, Brian O, additional, Rodríguez-García, Priscila M, additional, Rodríguez-Laboy, Abneris E, additional, Rodríguez-Santiago, Susana, additional, Rojas-Vargas, Michael L, additional, Rubio-Marrero, Eva N, additional, Santiago-Colón, Albeliz, additional, Santiago-Ortiz, Jorge L, additional, Santos-Ramos, Carlos E, additional, Serrano-González, Joseline, additional, Tamayo-Figueroa, Alina M, additional, Tascón-Peñaranda, Edna P, additional, Torres-Castillo, José L, additional, Valentín-Feliciano, Nelson A, additional, Valentín-Feliciano, Yashira M, additional, Vargas-Barreto, Nadyan M, additional, Vélez-Vázquez, Miguel, additional, Vilanova-Vélez, Luis R, additional, Zambrana-Echevarría, Cristina, additional, MacKinnon, Christy, additional, Chung, Hui-Min, additional, Kay, Chris, additional, Pinto, Anthony, additional, Kopp, Olga R, additional, Burkhardt, Joshua, additional, Harward, Chris, additional, Allen, Robert, additional, Bhat, Pavan, additional, Chang, Jimmy Hsiang-Chun, additional, Chen, York, additional, Chesley, Christopher, additional, Cohn, Dara, additional, DuPuis, David, additional, Fasano, Michael, additional, Fazzio, Nicholas, additional, Gavinski, Katherine, additional, Gebreyesus, Heran, additional, Giarla, Thomas, additional, Gostelow, Marcus, additional, Greenstein, Rachel, additional, Gunasinghe, Hashini, additional, Hanson, Casey, additional, Hay, Amanda, additional, He, Tao Jian, additional, Homa, Katie, additional, Howe, Ruth, additional, Howenstein, Jeff, additional, Huang, Henry, additional, Khatri, Aaditya, additional, Kim, Young Lu, additional, Knowles, Olivia, additional, Kong, Sarah, additional, Krock, Rebecca, additional, Kroll, Matt, additional, Kuhn, Julia, additional, Kwong, Matthew, additional, Lee, Brandon, additional, Lee, Ryan, additional, Levine, Kevin, additional, Li, Yedda, additional, Liu, Bo, additional, Liu, Lucy, additional, Liu, Max, additional, Lousararian, Adam, additional, Ma, Jimmy, additional, Mallya, Allyson, additional, Manchee, Charlie, additional, Marcus, Joseph, additional, McDaniel, Stephen, additional, Miller, Michelle L, additional, Molleston, Jerome M, additional, Diez, Cristina Montero, additional, Ng, Patrick, additional, Ngai, Natalie, additional, Nguyen, Hien, additional, Nylander, Andrew, additional, Pollack, Jason, additional, Rastogi, Suchita, additional, Reddy, Himabindu, additional, Regenold, Nathaniel, additional, Sarezky, Jon, additional, Schultz, Michael, additional, Shim, Jien, additional, Skorupa, Tara, additional, Smith, Kenneth, additional, Spencer, Sarah J, additional, Srikanth, Priya, additional, Stancu, Gabriel, additional, Stein, Andrew P, additional, Strother, Marshall, additional, Sudmeier, Lisa, additional, Sun, Mengyang, additional, Sundaram, Varun, additional, Tazudeen, Noor, additional, Tseng, Alan, additional, Tzeng, Albert, additional, Venkat, Rohit, additional, Venkataram, Sandeep, additional, Waldman, Leah, additional, Wang, Tracy, additional, Yang, Hao, additional, Yu, Jack Y, additional, Zheng, Yin, additional, Preuss, Mary L, additional, Garcia, Angelica, additional, Juergens, Matt, additional, Morris, Robert W, additional, Nagengast, Alexis A, additional, Azarewicz, Julie, additional, Carr, Thomas J, additional, Chichearo, Nicole, additional, Colgan, Mike, additional, Donegan, Megan, additional, Gardner, Bob, additional, Kolba, Nik, additional, Krumm, Janice L, additional, Lytle, Stacey, additional, MacMillian, Laurell, additional, Miller, Mary, additional, Montgomery, Andrew, additional, Moretti, Alysha, additional, Offenbacker, Brittney, additional, Polen, Mike, additional, Toth, John, additional, Woytanowski, John, additional, Kadlec, Lisa, additional, Crawford, Justin, additional, Spratt, Mary L, additional, Adams, Ashley L, additional, Barnard, Brianna K, additional, Cheramie, Martin N, additional, Eime, Anne M, additional, Golden, Kathryn L, additional, Hawkins, Allyson P, additional, Hill, Jessica E, additional, Kampmeier, Jessica A, additional, Kern, Cody D, additional, Magnuson, Emily E, additional, Miller, Ashley R, additional, Morrow, Cody M, additional, Peairs, Julia C, additional, Pickett, Gentry L, additional, Popelka, Sarah A, additional, Scott, Alexis J, additional, Teepe, Emily J, additional, TerMeer, Katie A, additional, Watchinski, Carmen A, additional, Watson, Lucas A, additional, Weber, Rachel E, additional, Woodard, Kate A, additional, Barnard, Daron C, additional, Appiah, Isaac, additional, Giddens, Michelle M, additional, McNeil, Gerard P, additional, Adebayo, Adeola, additional, Bagaeva, Kate, additional, Chinwong, Justina, additional, Dol, Chrystel, additional, George, Eunice, additional, Haltaufderhyde, Kirk, additional, Haye, Joanna, additional, Kaur, Manpreet, additional, Semon, Max, additional, Serjanov, Dmitri, additional, Toorie, Anika, additional, Wilson, Christopher, additional, Riddle, Nicole C, additional, Buhler, Jeremy, additional, Mardis, Elaine R, additional, and Elgin, Sarah C R, additional

Published
2015
Full Text
View/download PDF

43. Phosphorylation by Akt1 Promotes Skp2 Cytoplasmic Localization and Impairs APC/Cdh1-mediated Skp2 Destruction

Author

Gao, Daming, Inuzuka, Hiroyuki, Tseng, Alan, Chin, Rebecca Y., Toker, Alex, and Wei, Wenyi

Subjects
Article
Abstract

Deregulated Skp2 function promotes cell transformation, and this is consistent with observations of Skp2 over-expression in many human cancers. However, the mechanisms underlying elevated Skp2 expression remain elusive. Here we report that the serine/threonine protein kinase Akt1, but not Akt2, directly controls Skp2 stability by a mechanism that involves degradation by the APC/Cdh1 ubiquitin ligase complex. We further show that Akt1 phosphorylates Skp2 at Ser72, which is required to disrupt the interaction between Cdh1 and Skp2. In addition, we show that Ser72 is localized within a putative Nuclear Localization Sequence (NLS) and that phosphorylation of Ser72 by Akt leads to Skp2 cytoplasmic translocation. This finding expands our knowledge of how specific signaling kinase cascades influence proteolysis governed by APC/Cdh1 complexes, and provides evidence that elevated Akt activity and cytoplasmic Skp2 expression may be causative for cancer progression.

Published
2009

47. Investigating the Role of Akt1 in Prostate Cancer Development through Phosphorylation-dependent Regulation of Skp2 Stability and Oncogenic Function

Author

BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA, Wei, Wenyi, Gao, Daming, Inuzuka, Hiroyuki, Tseng, Alan, BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA, Wei, Wenyi, Gao, Daming, Inuzuka, Hiroyuki, and Tseng, Alan

Abstract

Elevated Skp2 expression is frequently observed in many tumors including breast and prostate carcinomas. However, the molecular mechanisms underlying elevated Skp2 expression in prostate cancers have not been fully explored. Hyperactivation of the Akt pathway is considered a hallmark of many cancers and it has been reported that activation of the PI3K/Akt pathway enhances p27 destruction. Thus, we hypothesize that sustained Akt activity in prostate cancer cells leads to elevated phosphorylation of Skp2, and subsequently influences Skp2 stability and its oncogenic functions. In support of our hypothesis, we found that Skp2 abundance is affected by manipulation of the PTEN/PI3K/Akt pathway in the PC3 and LNCaP prostate cancer cell lines. Furthermore, we showed that this is partially through phosphorylation of Skp2 by Akt, which impairs Skp2 destruction by Cdh1. Sequence analysis revealed that the Akt phosphorylation site (Ser72) is localized in a putative Nuclear Localization Sequence (NLS). Consistent with this notion, we found that overexpression of Myr-Akt promoted Skp2 cytoplasmic translocation, and that inhibition of PI3K/Akt activity enhanced its nuclear localization. We believe that these studies will provide a novel mechanism for Skp2 overexpression in prostate cancers and provide the rationale for developing Akt1-specific inhibitors to treat prostate cancer patients., The original document contains color images.

Published
2012

48. Investigating the Role of Akt1 in Prostate Cancer Development Through Phosphorylation-Dependent Regulation of Skp2 Stability and Oncogenic Function

Author

BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA, Gao, Daming, Inuzuka, Hiroyuki, Tseng, Alan, Wei, Wenyi, BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA, Gao, Daming, Inuzuka, Hiroyuki, Tseng, Alan, and Wei, Wenyi

Abstract

Elevated Skp2 expression is frequently observed in many tumors including breast and prostate carcinomas. However, the molecular mechanisms underlying elevated Skp2 expression in prostate cancers have not been fully explored. Hyperactivation of the Akt pathway is considered a hallmark of many cancers and it has been reported that activation of the PI3K/Akt pathway enhances p27 destruction. Thus, we hypothesize that sustained Akt activity in prostate cancer cells leads to elevated phosphorylation of Skp2, and subsequently influences Skp2 stability and its oncogenic functions. In support of our hypothesis, we found that Skp2 abundance is affected by manipulation of the PTEN/PI3K/Akt pathway in the PC3 and LNCaP prostate cancer cell lines. Furthermore, we showed that this is partially through phosphorylation of Skp2 by Akt, which impairs Skp2 destruction by Cdh1. Sequence analysis revealed that the Akt phosphorylation site (Ser72) is localized in a putative Nuclear Localization Sequence (NLS). Consistent with this notion, we found that overexpression of Myr-Akt promoted Skp2 cytoplasmic translocation, and that inhibition of PI3K/Akt activity enhanced its nuclear localization. We believe that these studies will provide a novel mechanism for Skp2 overexpression in prostate cancers and provide the rationale for developing Akt1-specific inhibitors to treat prostate cancer patients., The original document contains color images.

Published
2010

Catalog

Books, media, physical & digital resources
See catalog results