Literature DB >> 23641065

Regulation of mTORC1 and its impact on gene expression at a glance.

Mathieu Laplante1, David M Sabatini.   

Abstract

The mechanistic (or mammalian) target of rapamycin (mTOR) is a kinase that regulates key cellular functions linked to the promotion of cell growth and metabolism. This kinase, which is part of two protein complexes termed mTOR complex 1 (mTORC1) and 2 (mTORC2), has a fundamental role in coordinating anabolic and catabolic processes in response to growth factors and nutrients. Of the two mTOR complexes, mTORC1 is by far the best characterized. When active, mTORC1 triggers cell growth and proliferation by promoting protein synthesis, lipid biogenesis, and metabolism, and by reducing autophagy. The fact that mTORC1 deregulation is associated with several human diseases, such as type 2 diabetes, cancer, obesity and neurodegeneration, highlights its importance in the maintenance of cellular homeostasis. Over the last years, several groups observed that mTORC1 inhibition, in addition to reducing protein synthesis, deeply affects gene transcription. Here, we review the connections between mTORC1 and gene transcription by focusing on its impact in regulating the activation of specific transcription factors including including STAT3, SREBPs, PPARγ, PPARα, HIF1α, YY1–PGC1α and TFEB. We also discuss the importance of these transcription factors in mediating the effects of mTORC1 on various cellular processes in physiological and pathological contexts.

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Year:  2013        PMID: 23641065      PMCID: PMC3678406          DOI: 10.1242/jcs.125773

Source DB:  PubMed          Journal:  J Cell Sci        ISSN: 0021-9533            Impact factor:   5.285


  101 in total

Review 1.  SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver.

Authors:  Jay D Horton; Joseph L Goldstein; Michael S Brown
Journal:  J Clin Invest       Date:  2002-05       Impact factor: 14.808

2.  HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression.

Authors:  E Laughner; P Taghavi; K Chiles; P C Mahon; G L Semenza
Journal:  Mol Cell Biol       Date:  2001-06       Impact factor: 4.272

3.  Rapamycin-sensitive phase of 3T3-L1 preadipocyte differentiation after clonal expansion.

Authors:  A Gagnon; S Lau; A Sorisky
Journal:  J Cell Physiol       Date:  2001-10       Impact factor: 6.384

4.  Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR.

Authors:  K Yokogami; S Wakisaka; J Avruch; S A Reeves
Journal:  Curr Biol       Date:  2000-01-13       Impact factor: 10.834

Review 5.  Serine phosphorylation of STATs.

Authors:  T Decker; P Kovarik
Journal:  Oncogene       Date:  2000-05-15       Impact factor: 9.867

6.  TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling.

Authors:  Ken Inoki; Yong Li; Tianquan Zhu; Jun Wu; Kun-Liang Guan
Journal:  Nat Cell Biol       Date:  2002-09       Impact factor: 28.824

7.  The immunosuppressant rapamycin mimics a starvation-like signal distinct from amino acid and glucose deprivation.

Authors:  Tao Peng; Todd R Golub; David M Sabatini
Journal:  Mol Cell Biol       Date:  2002-08       Impact factor: 4.272

8.  Insulin stimulation of SREBP-1c processing in transgenic rat hepatocytes requires p70 S6-kinase.

Authors:  Joshua L Owen; Yuanyuan Zhang; Soo-Han Bae; Midhat S Farooqi; Guosheng Liang; Robert E Hammer; Joseph L Goldstein; Michael S Brown
Journal:  Proc Natl Acad Sci U S A       Date:  2012-08-27       Impact factor: 11.205

9.  Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival.

Authors:  Alejo Efeyan; Roberto Zoncu; Steven Chang; Iwona Gumper; Harriet Snitkin; Rachel L Wolfson; Oktay Kirak; David D Sabatini; David M Sabatini
Journal:  Nature       Date:  2012-12-23       Impact factor: 49.962

10.  Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway.

Authors:  Brendan D Manning; Andrew R Tee; M Nicole Logsdon; John Blenis; Lewis C Cantley
Journal:  Mol Cell       Date:  2002-07       Impact factor: 17.970

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  262 in total

Review 1.  Synchronizing transcriptional control of T cell metabolism and function.

Authors:  Kevin Man; Axel Kallies
Journal:  Nat Rev Immunol       Date:  2015-08-14       Impact factor: 53.106

2.  Inhibition of WNT-CTNNB1 signaling upregulates SQSTM1 and sensitizes glioblastoma cells to autophagy blockers.

Authors:  Mireia Nàger; Marta C Sallán; Anna Visa; Charumathi Pushparaj; Maria Santacana; Anna Macià; Andrée Yeramian; Carles Cantí; Judit Herreros
Journal:  Autophagy       Date:  2018-02-21       Impact factor: 16.016

3.  An integrative model for alternative polyadenylation, IntMAP, delineates mTOR-modulated endoplasmic reticulum stress response.

Authors:  Jae-Woong Chang; Wei Zhang; Hsin-Sung Yeh; Meeyeon Park; Chengguo Yao; Yongsheng Shi; Rui Kuang; Jeongsik Yong
Journal:  Nucleic Acids Res       Date:  2018-07-06       Impact factor: 16.971

Review 4.  Synaptic control of local translation: the plot thickens with new characters.

Authors:  María Gabriela Thomas; Malena Lucía Pascual; Darío Maschi; Luciana Luchelli; Graciela Lidia Boccaccio
Journal:  Cell Mol Life Sci       Date:  2013-11-10       Impact factor: 9.261

5.  Analysis of the uterine lumen in fertility-classified heifers: II. Proteins and metabolites†.

Authors:  Joao G N Moraes; Susanta K Behura; Jeanette V Bishop; Thomas R Hansen; Thomas W Geary; Thomas E Spencer
Journal:  Biol Reprod       Date:  2020-03-13       Impact factor: 4.285

Review 6.  MYC, Metabolism, and Cancer.

Authors:  Zachary E Stine; Zandra E Walton; Brian J Altman; Annie L Hsieh; Chi V Dang
Journal:  Cancer Discov       Date:  2015-09-17       Impact factor: 39.397

7.  Interferon regulatory factor 4 sustains CD8(+) T cell expansion and effector differentiation.

Authors:  Shuyu Yao; Bruno Fernando Buzo; Duy Pham; Li Jiang; Elizabeth J Taparowsky; Mark H Kaplan; Jie Sun
Journal:  Immunity       Date:  2013-11-07       Impact factor: 31.745

8.  mTOR signaling and transcriptional regulation in T lymphocytes.

Authors:  Hu Zeng; Hongbo Chi
Journal:  Transcription       Date:  2014

9.  MTOR-independent autophagy induced by interrupted endoplasmic reticulum-mitochondrial Ca2+ communication: a dead end in cancer cells.

Authors:  Ulises Ahumada-Castro; Eduardo Silva-Pavez; Alenka Lovy; Evelyn Pardo; Jordi Molgό; César Cárdenas
Journal:  Autophagy       Date:  2018-10-29       Impact factor: 16.016

10.  Insulin-induced de novo lipid synthesis occurs mainly via mTOR-dependent regulation of proteostasis of SREBP-1c.

Authors:  Qingming Dong; Gipsy Majumdar; Robert N O'Meally; Robert N Cole; Marshall B Elam; Rajendra Raghow
Journal:  Mol Cell Biochem       Date:  2019-09-20       Impact factor: 3.396

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