6 results on '"Maya Modak"'
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2. A protein interaction landscape of breast cancer
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Danielle L. Swaney, Kuei Ho Chen, Alan Ashworth, Morgan E. Diolaiti, Trey Ideker, Fan Zheng, Bing Xia, Kari A. Herrington, Beril Tutuncuoglu, Michael J. McGregor, John D. Gordan, Min-Kyu Kim, Mehdi Bouhaddou, Denise P. Muñoz, Denise M. Wolf, Erica Stevenson, Nevan J. Krogan, Margaret Soucheray, Tzeh Keong Foo, Patrick O’Leary, Ajda Rojc, Maya Modak, Kyumin Kim, Laura van 't Veer, Jean-Philippe Coppe, Jason F. Kreisberg, Jisoo Park, and Dominique C. Mitchell
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General Science & Technology ,Breast Neoplasms ,Biology ,Mass Spectrometry ,Article ,Cell Line ,Breast cancer ,Cell Line, Tumor ,Breast Cancer ,Genetics ,medicine ,Carcinoma ,2.1 Biological and endogenous factors ,Humans ,Protein Interaction Maps ,Aetiology ,Cancer ,Tandem affinity purification ,Tumor ,Multidisciplinary ,Tandem Affinity Purification ,Extramural ,A protein ,medicine.disease ,Neoplasm Proteins ,Cell culture ,Mutation (genetic algorithm) ,Mutation ,Cancer research ,Female ,Protein Interaction Map ,Biotechnology - Abstract
Mapping protein interactions driving cancer Cancer is a genetic disease, and much cancer research is focused on identifying carcinogenic mutations and determining how they relate to disease progression. Three papers demonstrate how mutations are processed through networks of protein interactions to promote cancer (see the Perspective by Cheng and Jackson). Swaney et al . focus on head and neck cancer and identify cancer-enriched interactions, demonstrating how point mutant–dependent interactions of PIK3CA, a kinase frequently mutated in human cancers, are predictive of drug response. Kim et al . focus on breast cancer and identify two proteins functionally connected to the tumor-suppressor gene BRCA1 and two proteins that regulate PIK3CA. Zheng et al . developed a statistical model that identifies protein networks that are under mutation pressure across different cancer types, including a complex bringing together PIK3CA with actomyosin proteins. These papers provide a resource that will be helpful in interpreting cancer genomic data. —VV
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- 2021
3. The Global Phosphorylation Landscape of SARS-CoV-2 Infection
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Yiming Cai, Maya Modak, Sebastian Weigang, Emmie de Wit, Jean K. Lim, Alistair Dunham, Benjamin J. Polacco, Qiongyu Li, Svenja Ulferts, Gwendolyn M. Jang, Aurelien Dugourd, David E. Gordon, Jeffrey Z. Guo, Kirsten Obernier, Sophia Bouhaddou, Elizabeth R. Fischer, Anna Gaulton, Jason C.J. Chang, Bjoern Meyer, Diego Quintero, Julian Knerr, Trupti Patil, Emma J. Manners, Michael C. O’Neal, Monita Muralidharan, Joseph Hiatt, Ajda Rojc, James E. Melnyk, Tanja Kortemme, Benjamin R. tenOever, Thomas Vallet, Rémy Robinot, Cassandra Koh, Benjamin E. Nilsson-Payant, Ruth Hüttenhain, Saker Klippsten, Alicia L. Richards, Eloy Felix, Brian K. Shoichet, Beril Tutuncuoglu, Danielle L. Swaney, Veronica V. Rezelj, Jeffery R. Johnson, Margaret Soucheray, Marisa Goff, R. Dyche Mullins, Kris M. White, Erica Stevenson, Jyoti Batra, Christopher J.P. Mathy, Yuan Zhou, Minkyu Kim, Marco Vignuzzi, Claudia Hernandez-Armenta, Kevan M. Shokat, Julio Saez-Rodriguez, Jacqueline M. Fabius, Timothy McBride, Adolfo García-Sastre, Quang Dinh Tran, Alexandra Hardy, Elena Moreno, Alberto Valdeolivas, Mehdi Bouhaddou, Andrew R. Leach, Melanie Ott, Georg Kochs, Pedro Beltrao, Jiewei Xu, Robyn M. Kaake, Merve Cakir, Ying Shi, Nevan J. Krogan, Lisa Miorin, Danish Memon, David J. Broadhurst, Miguel Correa Marrero, Robert Grosse, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Quantitative Biosciences Institute [UC San Francisco, USA] (QBI), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Gladstone Institutes [San Francisco], European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Populations virales et Pathogenèse - Viral Populations and Pathogenesis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Howard Hughes Medical Institute (HHMI), University of Freiburg [Freiburg], Virus et Immunité - Virus and immunity (CNRS-UMR3569), Universität Heidelberg [Heidelberg] = Heidelberg University, Heidelberg University Hospital [Heidelberg], Zoic Labs [Culver City, CA], Rocky Mountain Laboratories, Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre for Integrative Biological Signalling Studies [Freiburg] (CIBSS), This research was funded by grants from the National Institutes of Health ( P50AI150476 , U19AI135990 , U19AI135972 , R01AI143292 , R01AI120694 , P01A1063302 , and R01AI122747 to N.J.K., 1R01CA221969 and 1R01CA244550 to K.M.S., R01GM133981 to D.L.S., 1F32CA236347-01 to J.E.M., U19AI118610 to J.R.J., and F32CA239333 to M.B.), Defense Advance Research Projects Agency HR0011-19-2-0020 (to N.J.K., A.G.S., and K.M.S.), by the Laboratory for Genomics Research (LGR) Excellence in Research Award (ERA) from the Innovative Genomics Institute at UC Berkeley (grant number 133122P ), by CRIP (Center for Research for Influenza Pathogenesis), a NIAID-supported Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C ) (to A.G.S.), by supplements to NIAID grant U19AI135972 and DoD grant W81XWH-19-PRMRP-FPA (to A.G.S.), and by the generous support of the JPB Foundation , the Open Philanthropy Project (research grant 2020-215611 [5384] ), and other philanthropic donations (to A.G.S.), by the Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' grant ANR-10-LABX-62-IBEID (to M.V.), by the DFG under Germany's Excellence Strategy ( EXC-2189 , project ID 390939984 to R.G.), by a Starting Grant Award from the European Research Council ( ERC-2014-STG 638884 PhosFunc to P.B.), by the Federal Ministry of Education and Research (BMBF, Computational Life Sciences grant 031L0181B to J.S.R.), by the Intramural Research Program of the NIH, National Institute of Allergy and Infectious Diseases (to E.R.F. and E.D.W.), and by funding from F. Hoffmann-La Roche and Vir Biotechnology and gifts from The Ron Conway Family . K.M.S. is an investigator of the Howard Hughes Medical Institute., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 638884,H2020,ERC-2014-STG,PhosFunc(2015), Universität Heidelberg [Heidelberg], and Vaccine Research Institute (VRI)
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Proteomics ,MAPK/ERK pathway ,MESH: Angiotensin-Converting Enzyme 2 ,MESH: Casein Kinase II ,PIKFYVE ,0302 clinical medicine ,MESH: Chlorocebus aethiops ,MESH: Protein Kinase Inhibitors ,MESH: Animals ,Casein Kinase II ,Lung ,0303 health sciences ,Kinase ,MESH: Proteomics ,Phosphoproteomics ,antiviral ,Spike Glycoprotein ,Cyclin-Dependent Kinases ,3. Good health ,MESH: HEK293 Cells ,Spike Glycoprotein, Coronavirus ,Phosphorylation ,Infection ,MESH: Pandemics ,p38 mitogen-activated protein kinases ,Pneumonia, Viral ,MESH: Vero Cells ,p38 ,Antiviral Agents ,General Biochemistry, Genetics and Molecular Biology ,Article ,Betacoronavirus ,03 medical and health sciences ,Biodefense ,Humans ,MESH: SARS-CoV-2 ,MESH: Humans ,MESH: Phosphorylation ,Prevention ,MESH: Host-Pathogen Interactions ,fungi ,Receptor Protein-Tyrosine Kinases ,AXL ,Pneumonia ,Virology ,MAPK ,Coronavirus ,MESH: Peptidyl-Dipeptidase A ,MESH: Pneumonia, Viral ,MESH: Phosphatidylinositol 3-Kinases ,A549 Cells ,Vero cell ,Drug Evaluation ,030217 neurology & neurosurgery ,Developmental Biology ,MESH: Coronavirus Infections ,[SDV]Life Sciences [q-bio] ,viruses ,CDK ,Drug Evaluation, Preclinical ,MESH: Spike Glycoprotein, Coronavirus ,Medical and Health Sciences ,p38 Mitogen-Activated Protein Kinases ,Phosphatidylinositol 3-Kinases ,Chlorocebus aethiops ,MESH: COVID-19 ,Viral ,Phosphoinositide-3 Kinase Inhibitors ,mass spectrometry ,biology ,phosphoproteomics ,Biological Sciences ,Preclinical ,MESH: Cyclin-Dependent Kinases ,Infectious Diseases ,Host-Pathogen Interactions ,MESH: Betacoronavirus ,MESH: Drug Evaluation, Preclinical ,MESH: Receptor Protein-Tyrosine Kinases ,MESH: Caco-2 Cells ,Angiotensin-Converting Enzyme 2 ,Coronavirus Infections ,MESH: Antiviral Agents ,casein kinase II ,Peptidyl-Dipeptidase A ,Vaccine Related ,Cyclin-dependent kinase ,Proto-Oncogene Proteins ,Animals ,Pandemics ,Protein Kinase Inhibitors ,Vero Cells ,MESH: Phosphoinositide-3 Kinase Inhibitors ,030304 developmental biology ,SARS-CoV-2 ,COVID-19 ,Axl Receptor Tyrosine Kinase ,MESH: p38 Mitogen-Activated Protein Kinases ,MESH: Proto-Oncogene Proteins ,Emerging Infectious Diseases ,Good Health and Well Being ,HEK293 Cells ,biology.protein ,MESH: A549 Cells ,Caco-2 Cells - Abstract
Summary The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies., Graphical Abstract, Highlights • Phosphoproteomics analysis of SARS-CoV-2-infected cells uncovers signaling rewiring • Infection promotes host p38 MAPK cascade activity and shutdown of mitotic kinases • Infection stimulates CK2-containing filopodial protrusions with budding virus • Kinase activity analysis identifies potent antiviral drugs and compounds, Phosphoproteomics analysis of SARS-CoV-2-infected Vero E6 cells reveals host cellular pathways hijacked by viral infection, leading to the identification of small molecules that target dysregulated pathways and elicit potent antiviral efficacy.
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- 2020
4. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
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Pedro Beltrao, Phillip P. Sharp, Nevan J. Krogan, Sabrina J. Fletcher, Saker Klippsten, Trey Ideker, Melanie Ott, Bryan L. Roth, Xi Liu, Devin A. Cavero, Djoshkun Shengjuler, Christopher J.P. Mathy, Jason C.J. Chang, Theodore L. Roth, Hannes Braberg, Claudia Hernandez-Armenta, Lisa Miorin, Jyoti Batra, Shizhong Dai, Maliheh Safari, Brian K. Shoichet, Danish Memon, Tia A. Tummino, Marco Vignuzzi, Mark von Zastrow, Manon Eckhardt, Alan D. Frankel, Qiongyu Li, Tanja Kortemme, Nicole A. Wenzell, Zun Zar Chi Naing, Ferdinand Roesch, Nastaran Sadat Savar, Mathieu Hubert, Xi Ping Huang, Elena Moreno, Danica Galonić Fujimori, Jeffrey Z. Guo, Natalia Jura, Kirsten Obernier, Kliment A. Verba, Harmit S. Malik, Hao-Yuan Wang, Michael McGregor, Melanie J. Bennett, Julia Noack, Gwendolyn M. Jang, Paige Haas, Alice Mac Kain, Daniel J. Saltzberg, Mehdi Bouhaddou, Ziyang Zhang, Yongfeng Liu, Inigo Barrio-Hernandez, Yiming Cai, Kris M. White, Kelsey M. Haas, Maya Modak, Stephanie A. Wankowicz, Raphael Trenker, Kevan M. Shokat, Fatima S. Ugur, Shiming Peng, Sai J. Ganesan, Shaeri Mukherjee, Yuan Zhou, Minkyu Kim, John D. Gross, Jack Taunton, Alicia L. Richards, John S. Chorba, Margaret Soucheray, Danielle L. Swaney, Benjamin J. Polacco, Alan Ashworth, Wenqi Shen, Adolfo García-Sastre, Merve Cakir, Ujjwal Rathore, Kala Bharath Pilla, Michael C. O’Neal, Ying Shi, Kevin Lou, Cassandra Koh, Stephen N. Floor, Davide Ruggero, Ilsa T Kirby, Srivats Venkataramanan, Ruth Hüttenhain, Olivier Schwartz, Beril Tutuncuoglu, Christophe d'Enfert, Jose Liboy-Lugo, David A. Agard, Charles S. Craik, Veronica V. Rezelj, Tina Perica, Matthew P. Jacobson, Lorenzo Calviello, Eric Verdin, Yizhu Lin, Jiankun Lyu, Jiewei Xu, Joseph Hiatt, Andrej Sali, Oren S. Rosenberg, Markus Bohn, David E. Gordon, James S. Fraser, Sara Brin Rosenthal, Duygu Kuzuoğlu-Öztürk, Robyn M. Kaake, Jacqueline M. Fabius, Matthew J. O’Meara, Quang Dinh Tran, Advait Subramanian, Thomas Vallet, Bjoern Meyer, James E. Melnyk, Robert M. Stroud, Helene Foussard, Rakesh Ramachandran, David J. Broadhurst, Janet M. Young, and Michael Emerman
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0301 basic medicine ,viruses ,Drug Evaluation, Preclinical ,Plasma protein binding ,Proteomics ,medicine.disease_cause ,Mass Spectrometry ,0302 clinical medicine ,Chlorocebus aethiops ,Protein Interaction Mapping ,Molecular Targeted Therapy ,Protein Interaction Maps ,Cloning, Molecular ,Letter to the Editor ,Coronavirus ,Multidisciplinary ,3. Good health ,Drug repositioning ,030220 oncology & carcinogenesis ,Host-Pathogen Interactions ,Coronavirus Infections ,Protein Binding ,Pneumonia, Viral ,Biology ,Antiviral Agents ,Virus ,Betacoronavirus ,Viral Proteins ,03 medical and health sciences ,Immune system ,Protein Domains ,medicine ,Animals ,Humans ,Receptors, sigma ,Pandemics ,Vero Cells ,SKP Cullin F-Box Protein Ligases ,Innate immune system ,SARS-CoV-2 ,fungi ,HEK 293 cells ,Drug Repositioning ,COVID-19 ,Virology ,Immunity, Innate ,COVID-19 Drug Treatment ,HEK293 Cells ,030104 developmental biology ,Protein Biosynthesis - Abstract
A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein–protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19. A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.
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- 2020
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5. A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
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David E. Gordon, Gwendolyn M. Jang, Qiongyu Li, Natalia Jura, Sara Brin Rosenthal, Trey Ideker, Paige Haas, Melanie J. Bennett, Ilsa T Kirby, Adolfo García-Sastre, Michael Emerman, Thomas Vallet, Tina Perica, Lorenzo Calviello, Kirsten Obernier, Kliment A. Verba, Tanja Kortemme, Michael McGregor, Alan Ashworth, Ujjwal Rathore, Ziyang Zhang, Kelsey M. Haas, Rakesh Ramachandran, Mark von Zastrow, Jacqueline M. Fabius, Theodore L. Roth, Daniel J. Saltzberg, Matthew P. Jacobson, Kevin Lou, Ferdinand Roesch, Yizhu Lin, John S. Chorba, Beril Tutuncuoglu, Claudia Hernandez-Armenta, Harmit S. Malik, Janet M. Young, Manon Eckhardt, Srivats Venkataramanan, Jose Liboy-Lugo, Phillip P. Sharp, Jeffrey Z. Guo, Maya Modak, Shaeri Mukherjee, Markus Bohn, Brian K. Shoichet, Olivier Schwartz, Jiewei Xu, James S. Fraser, Andrej Sali, Oren S. Rosenberg, Christopher J.P. Mathy, Charles S. Craik, Benjamin J. Polacco, Melanie Ott, Sai J. Ganesan, Pedro Beltrao, Alicia L. Richards, Helene Foussard, Margaret Soucheray, Joseph Hiatt, Robyn M. Kaake, Danielle L. Swaney, Wenqi Shen, Bjoern Meyer, Kala Bharath Pilla, Zun Zar Chi Naing, Marco Vignuzzi, James E. Melnyk, John D. Gross, Shiming Peng, Mehdi Bouhaddou, Nevan J. Krogan, Merve Cakir, Mathieu Hubert, Stephanie A. Wankowicz, Ying Shi, Davide Ruggero, Kevan M. Shokat, Stephen N. Floor, Jack Taunton, Xi Liu, Ruth Hüttenhain, David A. Agard, Lisa Miorin, Danish Memon, Julia Noack, Raphael Trenker, Hannes Braberg, Shizhong Dai, Tia A. Tummino, Kris M. White, Yuan Zhou, Minkyu Kim, Devin A. Cavero, Jyoti Batra, Advait Subramanian, Danica Galonić Fujimori, and Inigo Barrio-Hernandez
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Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,media_common.quotation_subject ,viruses ,Host factors ,Article ,Vaccine Related ,03 medical and health sciences ,0302 clinical medicine ,Rare Diseases ,Biodefense ,2.2 Factors relating to the physical environment ,Aetiology ,Human proteins ,Lung ,030304 developmental biology ,media_common ,0303 health sciences ,Prevention ,Art ,Pneumonia ,3. Good health ,Good Health and Well Being ,Infectious Diseases ,Emerging Infectious Diseases ,5.1 Pharmaceuticals ,030220 oncology & carcinogenesis ,Protein Interaction Networks ,Molecular targets ,Pneumonia & Influenza ,Development of treatments and therapeutic interventions ,Infection ,Humanities - Abstract
Author(s): Gordon, David E; Jang, Gwendolyn M; Bouhaddou, Mehdi; Xu, Jiewei; Obernier, Kirsten; O'Meara, Matthew J; Guo, Jeffrey Z; Swaney, Danielle L; Tummino, Tia A; Huttenhain, Ruth; Kaake, Robyn M; Richards, Alicia L; Tutuncuoglu, Beril; Foussard, Helene; Batra, Jyoti; Haas, Kelsey; Modak, Maya; Kim, Minkyu; Haas, Paige; Polacco, Benjamin J; Braberg, Hannes; Fabius, Jacqueline M; Eckhardt, Manon; Soucheray, Margaret; Bennett, Melanie J; Cakir, Merve; McGregor, Michael J; Li, Qiongyu; Naing, Zun Zar Chi; Zhou, Yuan; Peng, Shiming; Kirby, Ilsa T; Melnyk, James E; Chorba, John S; Lou, Kevin; Dai, Shizhong A; Shen, Wenqi; Shi, Ying; Zhang, Ziyang; Barrio-Hernandez, Inigo; Memon, Danish; Hernandez-Armenta, Claudia; Mathy, Christopher JP; Perica, Tina; Pilla, Kala B; Ganesan, Sai J; Saltzberg, Daniel J; Ramachandran, Rakesh; Liu, Xi; Rosenthal, Sara B; Calviello, Lorenzo; Venkataramanan, Srivats; Lin, Yizhu; Wankowicz, Stephanie A; Bohn, Markus; Trenker, Raphael; Young, Janet M; Cavero, Devin; Hiatt, Joe; Roth, Theo; Rathore, Ujjwal; Subramanian, Advait; Noack, Julia; Hubert, Mathieu; Roesch, Ferdinand; Vallet, Thomas; Meyer, Bjorn; White, Kris M; Miorin, Lisa; Agard, David; Emerman, Michael; Ruggero, Davide; Garcia-Sastre, Adolfo; Jura, Natalia; von Zastrow, Mark; Taunton, Jack; Schwartz, Olivier; Vignuzzi, Marco; d'Enfert, Christophe; Mukherjee, Shaeri; Jacobson, Matt; Malik, Harmit S; Fujimori, Danica G; Ideker, Trey; Craik, Charles S | Abstract: An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity- purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.
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- 2020
6. Abstract 2308: The protein interaction landscape of breast cancer
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Trey Ideker, Kyumin Kim, Laura van 't Veer, Mehdi Bouhaddou, Danielle L. Swaney, Maya Modak, Denise M. Wolf, Alan Ashworth, Patrick O’Leary, Dominique C. Mitchell, John D. Gordan, Margaret Soucheray, Jisoo Park, Minkyu Kim, Fan Zheng, Jean-Philippe Coppe, Ajda Rojc, and Nevan J. Krogan
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Cancer Research ,Invasive carcinoma ,Cancer ,Biology ,medicine.disease ,Rare cancer ,Breast cancer ,Unknown Significance ,Oncology ,medicine ,Cancer research ,Interactor ,Breast cancer cells ,Protein kinase B - Abstract
Cancers have been associated with a diverse array of genomic alterations, many of which are rare with unknown significance. To understand the cellular mechanisms impacted by such alterations in breast invasive carcinoma, we have applied affinity-purification mass spectrometry to delineate comprehensive biophysical interaction networks for 40 frequently altered breast cancer proteins across three human breast cell lines, providing a novel resource of context-specific and shared protein-protein interaction networks in breast cancer cells. These networks interconnect and enrich for common and rare cancer mutations, and are substantially rewired by mutations. Our analysis identifies novel PIK3CA-interacting proteins which repress AKT signaling, and UBE2N emerges as a BRCA1 interactor predictive of clinical response to PARP inhibition. We also show that Spinophilin interacts with and dephosphorylates BRCA1 to promote DNA double-strand break repair. Thus, cancer protein interaction landscapes provide a framework for recognizing oncogenic drivers and drug vulnerabilities. Citation Format: Minkyu Kim, Jisoo Park, Mehdi Bouhaddou, Kyumin Kim, Ajda Rojc, Maya Modak, Margaret Soucheray, Patrick O'Leary, Denise Wolf, Dominique C. Mitchell, Fan Zheng, John D. Gordan, Jean-Philippe Coppé, Danielle L. Swaney, Laura van' t Veer, Alan Ashworth, Trey Ideker, Nevan J. Krogan. The protein interaction landscape of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2308.
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- 2021
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