Literature DB >> 25907074

mTOR activation is a biomarker and a central pathway to autoimmune disorders, cancer, obesity, and aging.

Andras Perl1,2.   

Abstract

The mechanistic target of rapamycin (mTOR) is a ubiquitous serine/threonine kinase, which plays pivotal roles in integrating growth signals on a cellular level. To support proliferation and survival under stress, two interacting complexes that harbor mTOR, mTORC1 and mTORC2, promote the transcription of genes involved in carbohydrate metabolism and lipogenesis, enhance protein translation, and inhibit autophagy. Although rapamycin was originally developed as an inhibitor of T cell proliferation for preventing organ transplant rejection, its molecular target, mTOR, has been subsequently identified as a central regulator of metabolic cues that drive lineage specification in the immune system. Owing to oxidative stress, the activation of mTORC1 has emerged as a central pathway for the pathogenesis of systemic lupus erythematosus and other autoimmune diseases. Paradoxically, mTORC1 has also been identified as a mediator of the Warburg effect that allows cell survival under hypoxia. Rapamycin and new classes of mTOR inhibitors are being developed to block not only transplant rejection and autoimmunity but also to treat obesity and various forms of cancer. Through preventing these diseases, personalized mTOR blockade holds promise to extend life span.
© 2015 New York Academy of Sciences.

Entities:  

Keywords:  T cell activation; autoimmunity; autophagy; biomarker; glutathione; glycolysis; hypoxia; inflammation; keloid disease; kynurenine; mTOR; metabolism; mitochondria; oxidative stress; pathogenesis; pentose phosphate pathway; rapamycin; sirolimus; systemic lupus erythematosus; treatment

Mesh:

Substances:

Year:  2015        PMID: 25907074      PMCID: PMC4480196          DOI: 10.1111/nyas.12756

Source DB:  PubMed          Journal:  Ann N Y Acad Sci        ISSN: 0077-8923            Impact factor:   5.691


  140 in total

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2.  Rapamycin-sensitive signals control TCR/CD28-driven Ifng, Il4 and Foxp3 transcription and promoter region methylation.

Authors:  Romana Tomasoni; Veronica Basso; Karolina Pilipow; Giovanni Sitia; Simona Saccani; Alessandra Agresti; Flore Mietton; Gioacchino Natoli; Sara Colombetti; Anna Mondino
Journal:  Eur J Immunol       Date:  2011-07       Impact factor: 5.532

3.  Metabolic programming and PDHK1 control CD4+ T cell subsets and inflammation.

Authors:  Valerie A Gerriets; Rigel J Kishton; Amanda G Nichols; Andrew N Macintyre; Makoto Inoue; Olga Ilkayeva; Peter S Winter; Xiaojing Liu; Bhavana Priyadharshini; Marta E Slawinska; Lea Haeberli; Catherine Huck; Laurence A Turka; Kris C Wood; Laura P Hale; Paul A Smith; Martin A Schneider; Nancie J MacIver; Jason W Locasale; Christopher B Newgard; Mari L Shinohara; Jeffrey C Rathmell
Journal:  J Clin Invest       Date:  2014-12-01       Impact factor: 14.808

4.  The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation.

Authors:  Ruoning Wang; Christopher P Dillon; Lewis Zhichang Shi; Sandra Milasta; Robert Carter; David Finkelstein; Laura L McCormick; Patrick Fitzgerald; Hongbo Chi; Joshua Munger; Douglas R Green
Journal:  Immunity       Date:  2011-12-23       Impact factor: 31.745

Review 5.  Current treatment strategies for inhibiting mTOR in cancer.

Authors:  Francesca Chiarini; Camilla Evangelisti; James A McCubrey; Alberto M Martelli
Journal:  Trends Pharmacol Sci       Date:  2014-12-11       Impact factor: 14.819

6.  Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue.

Authors:  Vanessa P Houde; Sophie Brûlé; William T Festuccia; Pierre-Gilles Blanchard; Kerstin Bellmann; Yves Deshaies; André Marette
Journal:  Diabetes       Date:  2010-03-18       Impact factor: 9.461

7.  Activation of mammalian target of rapamycin controls the loss of TCRzeta in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation.

Authors:  David R Fernandez; Tiffany Telarico; Eduardo Bonilla; Qing Li; Sanjay Banerjee; Frank A Middleton; Paul E Phillips; Mary K Crow; Stefanie Oess; Werner Muller-Esterl; Andras Perl
Journal:  J Immunol       Date:  2009-02-15       Impact factor: 5.422

8.  Incidence and risk of treatment-related mortality with mTOR inhibitors everolimus and temsirolimus in cancer patients: a meta-analysis.

Authors:  Wei-Xiang Qi; Yu-Jing Huang; Yang Yao; Zan Shen; Da-Liu Min
Journal:  PLoS One       Date:  2013-06-13       Impact factor: 3.240

9.  Rapid non-genomic signalling by 17β-oestradiol through c-Src involves mTOR-dependent expression of HIF-1α in breast cancer cells.

Authors:  S Sudhagar; S Sathya; B S Lakshmi
Journal:  Br J Cancer       Date:  2011-09-06       Impact factor: 7.640

10.  PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells.

Authors:  David K Finlay; Ella Rosenzweig; Linda V Sinclair; Carmen Feijoo-Carnero; Jens L Hukelmann; Julia Rolf; Andrey A Panteleyev; Klaus Okkenhaug; Doreen A Cantrell
Journal:  J Exp Med       Date:  2012-11-26       Impact factor: 14.307

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  81 in total

Review 1.  Immune senescence, epigenetics and autoimmunity.

Authors:  Donna Ray; Raymond Yung
Journal:  Clin Immunol       Date:  2018-04-11       Impact factor: 3.969

2.  The influence of pro-longevity gene Gclc overexpression on the age-dependent changes in Drosophila transcriptome and biological functions.

Authors:  Alexey Moskalev; Mikhail Shaposhnikov; Ekaterina Proshkina; Alexey Belyi; Alexander Fedintsev; Svetlana Zhikrivetskaya; Zulfiya Guvatova; Asiya Sadritdinova; Anastasia Snezhkina; George Krasnov; Anna Kudryavtseva
Journal:  BMC Genomics       Date:  2016-12-28       Impact factor: 3.969

3.  Age-associated DNA methylation changes in naive CD4+ T cells suggest an evolving autoimmune epigenotype in aging T cells.

Authors:  Mikhail G Dozmorov; Patrick Coit; Kathleen Maksimowicz-McKinnon; Amr H Sawalha
Journal:  Epigenomics       Date:  2017-03-21       Impact factor: 4.778

4.  Systemic lupus erythematosus-myasthenia gravis overlap syndrome: Presentation and treatment depend on prior thymectomy.

Authors:  Scott Brian Minchenberg; Geeta Chaparala; Zachary Oaks; Katalin Banki; Andras Perl
Journal:  Clin Immunol       Date:  2018-07-17       Impact factor: 3.969

5.  Phosphorylated mTOR and YAP serve as prognostic markers and therapeutic targets in gliomas.

Authors:  Mei Liu; Yong Lin; Xian-Chao Zhang; Yu-Huan Tan; Yue-Liang Yao; Juan Tan; Xia Zhang; You-Hong Cui; Xindong Liu; Yan Wang; Xiu-Wu Bian
Journal:  Lab Invest       Date:  2017-07-31       Impact factor: 5.662

6.  Amino Acids Regulate mTORC1 by an Obligate Two-step Mechanism.

Authors:  Julia Dyachok; Svetlana Earnest; Erica N Iturraran; Melanie H Cobb; Elliott M Ross
Journal:  J Biol Chem       Date:  2016-09-01       Impact factor: 5.157

7.  Splicing factor SRSF1 controls T cell hyperactivity and systemic autoimmunity.

Authors:  Takayuki Katsuyama; Hao Li; Denis Comte; George C Tsokos; Vaishali R Moulton
Journal:  J Clin Invest       Date:  2019-12-02       Impact factor: 14.808

8.  Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway.

Authors:  Asif Elahi; Subrata Sabui; Nell N Narasappa; Sudhanshu Agrawal; Nils W Lambrecht; Anshu Agrawal; Hamid M Said
Journal:  J Immunol       Date:  2018-03-12       Impact factor: 5.422

9.  Genistein protects against ox-LDL-induced senescence through enhancing SIRT1/LKB1/AMPK-mediated autophagy flux in HUVECs.

Authors:  Huaping Zhang; Xiaorong Yang; Xuefen Pang; Zhenxiang Zhao; Haixia Yu; Hui Zhou
Journal:  Mol Cell Biochem       Date:  2018-11-16       Impact factor: 3.396

Review 10.  Moving towards personalized treatments of immune-related adverse events.

Authors:  Khashayar Esfahani; Arielle Elkrief; Cassandra Calabrese; Réjean Lapointe; Marie Hudson; Bertrand Routy; Wilson H Miller; Leonard Calabrese
Journal:  Nat Rev Clin Oncol       Date:  2020-04-03       Impact factor: 66.675

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