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252. mTORC1 and mTORC2 in energy homeostasis

Author

Cornu Marion and Hall Michael N

Abstract

This volume of The Enzymes features high caliber thematic articles on the topic of glycosylphopshatidylinositol (GPI) anchoring of proteins. Contributions from leading authorities Informs and updates on all the latest developments in ...

Published
2010

255. TOR complexes: composition, structure and phosphorylation

Author

Zinzalla Vittoria, Sturgill Thomas W, and Hall Michael N

Abstract

There has been an explosion of knowledge in this area in recent years and this volume provides an in depth review of our current knowledge of TOR complexes by the leaders in the field. Contributions from leading authorities Informs and ...

Published
2010

259. Raptor ablation in skeletal muscle decreases Cav1.1 expression and affects the function of the excitation–contraction coupling supramolecular complex

Author

Lopez, Rubén J., primary, Mosca, Barbara, additional, Treves, Susan, additional, Maj, Marcin, additional, Bergamelli, Leda, additional, Calderon, Juan C., additional, Bentzinger, C. Florian, additional, Romanino, Klaas, additional, Hall, Michael N., additional, Rüegg, Markus A., additional, Delbono, Osvaldo, additional, Caputo, Carlo, additional, and Zorzato, Francesco, additional

Published
2015
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260. Rank Difference Analysis of Microarrays (RDAM), a novel approach to statistical analysis of microarray expression profiling data

Author

Martin, Dietmar E, Demougin, Philippe, Hall, Michael N, and Bellis, Michel

Subjects
lcsh:Biology (General), Methodology Article, Gene Expression Profiling, lcsh:R858-859.7, lcsh:Computer applications to medicine. Medical informatics, lcsh:QH301-705.5, Oligonucleotide Array Sequence Analysis
Abstract

Background A key step in the analysis of microarray expression profiling data is the identification of genes that display statistically significant changes in expression signals between two biological conditions. Results We describe a new method, Rank Difference Analysis of Microarrays (RDAM), which estimates the total number of truly varying genes and assigns a p-value to each signal variation. Information on a group of differentially expressed genes includes the sensitivity and the false discovery rate. We demonstrate the feasibility and efficiency of our approach by applying it to a large synthetic expression data set and to a biological data set obtained by comparing vegetatively-growing wild type and tor2-mutant yeast strains. In both cases we observed a significant improvement of the power of analysis when our method is compared to another popular nonparametric method. Conclusions This study provided a valuable new statistical method to analyze microarray data. We conclude that the good quality of the results obtained by RDAM is mainly due to the quasi-perfect equalization of variation distribution, which is related to the standardization procedure used and to the measurement of variation by rank difference.

Published
2004

263. mTORC1 Controls PNS Myelination along the mTORC1-RXR gamma-SREBP-Lipid Biosynthesis Axis in Schwann Cells

Author

University of Helsinki, Lääketieteellisen tiedekunnan muu toiminta (-2009), University of Helsinki, Research Programs Unit, Norrmen, Camilla, Figlia, Gianluca, Lebrun-Julien, Frederic, Pereira, Jorge A., Troetzmueller, Martin, Koefeler, Harald C., Rantanen, Ville, Wessig, Carsten, van Deijk, Anne-Lieke F., Smit, August B., Verheijen, Mark H. G., Rueegg, Markus A., Hall, Michael N., Suter, Ueli, University of Helsinki, Lääketieteellisen tiedekunnan muu toiminta (-2009), University of Helsinki, Research Programs Unit, Norrmen, Camilla, Figlia, Gianluca, Lebrun-Julien, Frederic, Pereira, Jorge A., Troetzmueller, Martin, Koefeler, Harald C., Rantanen, Ville, Wessig, Carsten, van Deijk, Anne-Lieke F., Smit, August B., Verheijen, Mark H. G., Rueegg, Markus A., Hall, Michael N., and Suter, Ueli

Published
2014

264. mTORC1-mediated translational elongation limits intestinal tumour initiation and growth

Author

Faller, William J., primary, Jackson, Thomas J., additional, Knight, John R. P., additional, Ridgway, Rachel A., additional, Jamieson, Thomas, additional, Karim, Saadia A., additional, Jones, Carolyn, additional, Radulescu, Sorina, additional, Huels, David J., additional, Myant, Kevin B., additional, Dudek, Kate M., additional, Casey, Helen A., additional, Scopelliti, Alessandro, additional, Cordero, Julia B., additional, Vidal, Marcos, additional, Pende, Mario, additional, Ryazanov, Alexey G., additional, Sonenberg, Nahum, additional, Meyuhas, Oded, additional, Hall, Michael N., additional, Bushell, Martin, additional, Willis, Anne E., additional, and Sansom, Owen J., additional

Published
2014
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269. mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress

Author

Grahammer, Florian, primary, Haenisch, Nora, additional, Steinhardt, Frederic, additional, Sandner, Lukas, additional, Roerden, Malte, additional, Arnold, Frederic, additional, Cordts, Tomke, additional, Wanner, Nicola, additional, Reichardt, Wilfried, additional, Kerjaschki, Dontscho, additional, Ruegg, Markus A., additional, Hall, Michael N., additional, Moulin, Pierre, additional, Busch, Hauke, additional, Boerries, Melanie, additional, Walz, Gerd, additional, Artunc, Ferruh, additional, and Huber, Tobias B., additional

Published
2014
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273. Homeo domain of the yeast repressor alpha 2 is a sequence-specific DNA-binding domain but is not sufficient for repression

Author

Hall, Michael N. and Johnson, Alexander D.

Subjects
Analysis, Research, Drosophila -- Research -- Analysis, Protein binding -- Research -- Analysis, Protein research -- Analysis -- Research, Genetic research -- Analysis
Abstract

Homeo Domain of the Yeast Repressor 2 Is a Sequence-Specific DNA-Binding Domain But Is Not Sufficient for Repression THE 2 PROTEIN, THE PRODUCT OF THE MAT 2 GENE, IS an [...]

Published
1987

274. mTOR signalling and cellular metabolism are mutual determinants in cancer

Author

Mossmann, Dirk, Park, Sujin, and Hall, Michael N.

Abstract

Oncogenic signalling and metabolic alterations are interrelated in cancer cells. mTOR, which is frequently activated in cancer, controls cell growth and metabolism. mTOR signalling regulates amino acid, glucose, nucleotide, fatty acid and lipid metabolism. Conversely, metabolic inputs, such as amino acids, activate mTOR. In this Review, we discuss how mTOR signalling rewires cancer cell metabolism and delineate how changes in metabolism, in turn, sustain mTOR signalling and tumorigenicity. Several drugs are being developed to perturb cancer cell metabolism. However, their efficacy as stand-alone therapies, similar to mTOR inhibitors, is limited. Here, we discuss how the interdependence of mTOR signalling and metabolism can be exploited for cancer therapy.

Published
2018
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275. The protein histidine phosphatase LHPP is a tumour suppressor

Author

Hindupur, Sravanth K., Colombi, Marco, Fuhs, Stephen R., Matter, Matthias S., Guri, Yakir, Adam, Kevin, Cornu, Marion, Piscuoglio, Salvatore, Ng, Charlotte K. Y., Betz, Charles, Liko, Dritan, Quagliata, Luca, Moes, Suzette, Jenoe, Paul, Terracciano, Luigi M., Heim, Markus H., Hunter, Tony, and Hall, Michael N.

Abstract

Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated. Conversely, expression of the putative histidine phosphatase LHPP was downregulated specifically in the tumours. We demonstrate that LHPP is indeed a protein histidine phosphatase. Consistent with these observations, global histidine phosphorylation was significantly upregulated in the liver tumours. Sustained, hepatic expression of LHPP in the hepatocellular carcinoma mouse model reduced tumour burden and prevented the loss of liver function. Finally, in patients with hepatocellular carcinoma, low expression of LHPP correlated with increased tumour severity and reduced overall survival. Thus, LHPP is a protein histidine phosphatase and tumour suppressor, suggesting that deregulated histidine phosphorylation is oncogenic.

Published
2018
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276. Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells : erratum (Cell 154, 859–874; August 15, 2013)

Author

Thedieck, Kathrin, Holzwarth, Birgit, Prentzell, Mirja Tamara, Boehlke, Christopher, Kläsener, Kathrin, Ruf, Stefanie, Sonntag, Annika Gwendolin, Maerz, Lars, Grellscheid, Sushma-Nagaraja, Kremmer, Elisabeth, Nitschke, Roland, Kuehn, E. Wolfgang, Jonker, Johan W., Groen, Albert K., Reth, Michael, Hall, Michael N., Baumeister, Ralf, Thedieck, Kathrin, Holzwarth, Birgit, Prentzell, Mirja Tamara, Boehlke, Christopher, Kläsener, Kathrin, Ruf, Stefanie, Sonntag, Annika Gwendolin, Maerz, Lars, Grellscheid, Sushma-Nagaraja, Kremmer, Elisabeth, Nitschke, Roland, Kuehn, E. Wolfgang, Jonker, Johan W., Groen, Albert K., Reth, Michael, Hall, Michael N., and Baumeister, Ralf

Published
2013

277. Inhibition of mTORC1 by astrin and stress granules prevents apoptosis in cancer cells.

Author

Thedieck, Kathrin, Holzwarth, Birgit, Prentzell, Mirja Tamara, Boehlke, Christopher, Kläsener, Kathrin, Ruf, Stefanie, Sonntag, Annika Gwendolin, Maerz, Lars, Grellscheid, Sushma-Nagaraja, Kremmer, Elisabeth, Nitschke, Roland, Kuehn, E. Wolfgang, Jonker, Johan W., Groen, Albert K., Reth, Michael, Hall, Michael N., Baumeister, Ralf, Thedieck, Kathrin, Holzwarth, Birgit, Prentzell, Mirja Tamara, Boehlke, Christopher, Kläsener, Kathrin, Ruf, Stefanie, Sonntag, Annika Gwendolin, Maerz, Lars, Grellscheid, Sushma-Nagaraja, Kremmer, Elisabeth, Nitschke, Roland, Kuehn, E. Wolfgang, Jonker, Johan W., Groen, Albert K., Reth, Michael, Hall, Michael N., and Baumeister, Ralf

Published
2013

278. TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis

Author

Shimobayashi, Mitsugu, Oppliger, Wolfgang, Moes, Suzette, Jenö, Paul, Hall, Michael N, Shimobayashi, Mitsugu, Oppliger, Wolfgang, Moes, Suzette, Jenö, Paul, and Hall, Michael N

Abstract

The evolutionarily conserved Orm1 and Orm2 proteins mediate sphingolipid homeostasis. However, the homologous Orm proteins and the signaling pathways modulating their phosphorylation and function are incompletely characterized. Here we demonstrate that inhibition of nutrient-sensitive target of rapamycin complex 1 (TORC1) stimulates Orm phosphorylation and synthesis of complex sphingolipids in Saccharomyces cerevisiae. TORC1 inhibition activates the kinase Npr1 that directly phosphorylates and activates the Orm proteins. Npr1-phosphorylated Orm1 and Orm2 stimulate de novo synthesis of complex sphingolipids downstream of serine palmitoyltransferase. Complex sphingolipids in turn stimulate plasma membrane localization and activity of the nutrient scavenging general amino acid permease 1. Thus activation of Orm and complex sphingolipid synthesis upon TORC1 inhibition is a physiological response to starvation.

Published
2013

279. Evolution of TOR and Translation Control.

Author

Fonseca, Bruno D., Graber, Tyson E., Hoang, Huy-Dung, González, Asier, Soukas, Alexandre A., Hernández, Greco, Alain, Tommy, Swift, Stephanie L., Weisman, Ronit, Meyer, Christian, Robaglia, Christophe, Avruch, Joseph, and Hall, Michael N.

Published
2016
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282. Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control

Author

Loewith, Robbie, Hall, Michael N, Loewith, Robbie, and Hall, Michael N

Abstract

TOR (Target Of Rapamycin) is a highly conserved protein kinase that is important in both fundamental and clinical biology. In fundamental biology, TOR is a nutrient-sensitive, central controller of cell growth and aging. In clinical biology, TOR is implicated in many diseases and is the target of the drug rapamycin used in three different therapeutic areas. The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function. Here we review the TOR signaling network in S. cerevisiae.

Published
2011

283. Impact papers on aging in 2009.

Author

Blagosklonny, Mikhail V, Blagosklonny, Mikhail V, Campisi, Judy, Sinclair, David A, Bartke, Andrzej, Blasco, Maria A, Bonner, William M, Bohr, Vilhelm A, Brosh, Robert M, Brunet, Anne, Depinho, Ronald A, Donehower, Lawrence A, Finch, Caleb E, Finkel, Toren, Gorospe, Myriam, Gudkov, Andrei V, Hall, Michael N, Hekimi, Siegfried, Helfand, Stephen L, Karlseder, Jan, Kenyon, Cynthia, Kroemer, Guido, Longo, Valter, Nussenzweig, Andre, Osiewacz, Heinz D, Peeper, Daniel S, Rando, Thomas A, Rudolph, K Lenhard, Sassone-Corsi, Paolo, Serrano, Manuel, Sharpless, Norman E, Skulachev, Vladimir P, Tilly, Jonathan L, Tower, John, Verdin, Eric, Vijg, Jan, Blagosklonny, Mikhail V, Blagosklonny, Mikhail V, Campisi, Judy, Sinclair, David A, Bartke, Andrzej, Blasco, Maria A, Bonner, William M, Bohr, Vilhelm A, Brosh, Robert M, Brunet, Anne, Depinho, Ronald A, Donehower, Lawrence A, Finch, Caleb E, Finkel, Toren, Gorospe, Myriam, Gudkov, Andrei V, Hall, Michael N, Hekimi, Siegfried, Helfand, Stephen L, Karlseder, Jan, Kenyon, Cynthia, Kroemer, Guido, Longo, Valter, Nussenzweig, Andre, Osiewacz, Heinz D, Peeper, Daniel S, Rando, Thomas A, Rudolph, K Lenhard, Sassone-Corsi, Paolo, Serrano, Manuel, Sharpless, Norman E, Skulachev, Vladimir P, Tilly, Jonathan L, Tower, John, Verdin, Eric, and Vijg, Jan

Abstract

The Editorial Board of Aging reviews research papers published in 2009, which they believe have or will have significant impact on aging research. Among many others, the topics include genes that accelerate aging or in contrast promote longevity in model organisms, DNA damage responses and telomeres, molecular mechanisms of life span extension by calorie restriction and pharmacological interventions into aging. The emerging message in 2009 is that aging is not random but determined by a genetically-regulated longevity network and can be decelerated both genetically and pharmacologically.

Published
2010

284. Impact papers on aging in 2009

Author

Blagosklonny, Mikhail V., Campisi, Judy, Sinclair, David A., Bartke, Andrzej, Blasco, Maria A., Bonner, William M., Bohr, Vilhelm A., Brosh, Robert M., Brunet, Anne, DePinho, Ronald A., Donehower, Lawrence A., Finch, Caleb E., Finkel, Toren, Gorospe, Myriam, Gudkov, Andrei V., Hall, Michael N., Hekimi, Siegfried, Helfand, Stephen L., Karlseder, Jan, Kenyon, Cynthia, Kroemer, Guido, Longo, Valter, Nussenzweig, Andre, Osiewacz, Heinz D., Peeper, Daniel S., Rando, Thomas A., Rudolph, K. Lenhard, Sassone-Corsi, Paolo, Serrano, Manuel, Sharpless, Norman E., Skulachev, Vladimir P., Tilly, Jonathan L., Tower, John, Verdin, Eric, Vijg, Jan, Blagosklonny, Mikhail V., Campisi, Judy, Sinclair, David A., Bartke, Andrzej, Blasco, Maria A., Bonner, William M., Bohr, Vilhelm A., Brosh, Robert M., Brunet, Anne, DePinho, Ronald A., Donehower, Lawrence A., Finch, Caleb E., Finkel, Toren, Gorospe, Myriam, Gudkov, Andrei V., Hall, Michael N., Hekimi, Siegfried, Helfand, Stephen L., Karlseder, Jan, Kenyon, Cynthia, Kroemer, Guido, Longo, Valter, Nussenzweig, Andre, Osiewacz, Heinz D., Peeper, Daniel S., Rando, Thomas A., Rudolph, K. Lenhard, Sassone-Corsi, Paolo, Serrano, Manuel, Sharpless, Norman E., Skulachev, Vladimir P., Tilly, Jonathan L., Tower, John, Verdin, Eric, and Vijg, Jan

Abstract

The editorial board of Aging reviews research papers published in 2009,which they believe have or will have a significant impact on aging research.Among many others, the topics include genes that accelerate aging or incontrast promote longevity in model organisms, DNA damage responsesand telomeres, molecular mechanisms of life span extension by calorierestriction and pharmacologic interventions into aging. The emergingmessage in 2009 is that aging is not random but determined by agenetically-regulated longevity network and can be decelerated bothgenetically and pharmacologically.

Published
2010

285. The Rapamycin-sensitive Phosphoproteome Reveals That TOR Controls Protein Kinase A Toward Some But Not All Substrates

Author

Soulard, Alexandre, Cremonesi, Alessio; https://orcid.org/0000-0002-1524-4169, Moes, Suzette, Schütz, Frédéric, Jenö, Paul, Hall, Michael N, Soulard, Alexandre, Cremonesi, Alessio; https://orcid.org/0000-0002-1524-4169, Moes, Suzette, Schütz, Frédéric, Jenö, Paul, and Hall, Michael N

Abstract

Regulation of cell growth requires extensive coordination of several processes including transcription, ribosome biogenesis, translation, nutrient metabolism, and autophagy. In yeast, the protein kinases Target of Rapamycin (TOR) and protein kinase A (PKA) regulate these processes and are thereby the main activators of cell growth in response to nutrients. How TOR, PKA, and their corresponding signaling pathways are coordinated to control the same cellular processes is not understood. Quantitative analysis of the rapamycin-sensitive phosphoproteome combined with targeted analysis of PKA substrates suggests that TOR complex 1 (TORC1) activates PKA but only toward a subset of substrates. Furthermore, we show that TORC1 signaling impinges on BCY1, the negative regulatory subunit of PKA. Inhibition of TORC1 with rapamycin leads to BCY1 phosphorylation on several sites including T129. Phosphorylation of BCY1 T129 results in BCY1 activation and inhibition of PKA. TORC1 inhibits BCY1 T129 phosphorylation by phosphorylating and activating the S6K homolog SCH9 that in turn inhibits the MAP kinase MPK1. MPK1 phosphorylates BCY1 T129 directly. Thus, TORC1 activates PKA toward some substrates by preventing MPK1-mediated activation of BCY1.

Published
2010

286. The Search for Anti-Inflammatory Drugs

Author

Hall, Michael N.

Subjects
The Search for Anti-Inflammatory Drugs (Book) -- Book reviews, Books -- Book reviews, Biological sciences, Chemistry
Published
1996

289. WNT7B Promotes Bone Formation in part through mTORC1

Author

Chen, Jianquan, primary, Tu, Xiaolin, additional, Esen, Emel, additional, Joeng, Kyu Sang, additional, Lin, Congxin, additional, Arbeit, Jeffrey M., additional, Rüegg, Markus A., additional, Hall, Michael N., additional, Ma, Liang, additional, and Long, Fanxin, additional

Published
2014
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291. An Isogenic Cell Panel Identifies Compounds That Inhibit Proliferation of mTOR-Pathway Addicted Cells by Different Mechanisms

Author

Wyder Peters, Lorenza, primary, Molle, Klaus D., additional, Thiemeyer, Anke, additional, Knopf, Agnes, additional, Goxe, Marie, additional, Guerry, Philippe, additional, Brodbeck, Daniela, additional, Colombi, Marco, additional, Hall, Michael N., additional, Moroni, Christoph, additional, and Regenass, Urs, additional

Published
2014
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292. List of Contributors

Author

Adams, Michelle M., Ainslie, Garrett R., Ambrósio, António Francisco, Arent, Camila O., Athira, A.P., Baar, Keith, Doldur-Balli, Fusun, Bazer, Fuller W., Beckley, Jacob T., Bhattacharya, Shelley, Bilan, Agnès Rioux, Binu, S., Celebi-Birand, Ergul Dilan, Cai, Zhiyou, Calon, Frédéric, Castellanos, Mar, Chatterjee, Sarmishtha, Citraro, Rita, Constanti, Andrew, Coppola, Antonietta, Das, Anindita, De Sarro, Giovambattista, Fauconneau, Bernard, Fernandes, Rosa, Francois, Arnaud, Gibson, K. Michael, Giovannini, Maria Grazia, Glasgow, Connie G., Gubern, Carme, Hall, Michael N., Hughes, David C., Inoue, Ken-ichi, Janet, Thierry, Kadar, Elisabet, Kapoor, Mohit, Karoglu, Elif Tugce, Kato, Hiroshi, Klintmalm, Goran B.G., Kubota, Keiichi, Kukreja, Rakesh C., Lana, Daniele, Leo, Antonio, Lisi, Lucia, Liu, Xiangwei, Maiese, Kenneth, Massari, Francesco, McKenna, Greg J., Moss, Joel, Munshi, Chayan, Nakamura, Akihiro, Navarra, Pierluigi, Paccalin, Marc, Pacheco-Rodriguez, Gustavo, Page, Guylène, Palavra, Filipe, Perl, Andras, Pitcher, Meagan R., Quevedo, João, Reis, Flávio, Ren, Jun, Réus, Gislaine Z., Ron, Dorit, Russo, Cinzia Dello, Russo, Emilio, Santoni, Matteo, Shibuya, Norisuke, Soumya, S.J., Steagall, Wendy K., Sudhakaran, P.R., Swierczynska, Marta M., Verite, Julie, Vogel, Kara R., Wallace, Marita A., Wang, Xiaoqiu, Wu, Guoyao, and Yan, Liang-Jun

Published
2016
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294. Inhibition of mTORC1 by Astrin and Stress Granules Prevents Apoptosis in Cancer Cells

Author

Thedieck, Kathrin, primary, Holzwarth, Birgit, additional, Prentzell, Mirja Tamara, additional, Boehlke, Christopher, additional, Kläsener, Kathrin, additional, Ruf, Stefanie, additional, Sonntag, Annika Gwendolin, additional, Maerz, Lars, additional, Grellscheid, Sushma-Nagaraja, additional, Kremmer, Elisabeth, additional, Nitschke, Roland, additional, Kuehn, E. Wolfgang, additional, Jonker, Johan W., additional, Groen, Albert K., additional, Reth, Michael, additional, Hall, Michael N., additional, and Baumeister, Ralf, additional

Published
2013
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