Inhibition of mammalian target of rapamycin activates apoptosis signal-regulating kinase 1 signaling by suppressing protein phosphatase 5 activity.

The Journal of Biological Chemistry
Shile HuangPeter J Houghton

Abstract

Under serum-free conditions, rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), induces a cellular stress response characterized by rapid and sustained activation of the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway and selective apoptosis of cells lacking functional p53. Here we have investigated how mTOR regulates ASK1 signaling using p53-mutant rhabdomyosarcoma cells. In Rh30 cells, ASK1 was found to physically interact with protein phosphatase 5 (PP5), previously identified as a negative regulator of ASK1. Rapamycin did not affect either protein level of PP5 or association of PP5 with ASK1. Instead, rapamycin caused rapid dissociation of the PP2A-B" regulatory subunit (PR72) from the PP5-ASK1 complex, which was associated with reduced phosphatase activity of PP5. This effect was dependent on expression of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Down-regulation of PP5 activity by rapamycin coordinately activated ASK1, leading to elevated phosphorylation of c-Jun. Amino acid deprivation, which like rapamycin inhibits mTOR signaling, also inhibited PP5 activity, caused rapid dissociation of PR72, and activated ASK1 signaling. Overexpression of PP5, but not the PP2A catalytic su...Continue Reading

References

May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·J ChenS L Schreiber
Nov 8, 1994·Proceedings of the National Academy of Sciences of the United States of America·M Chinkers
Nov 15, 1996·The Journal of Clinical Investigation·M PoonA R Marks
Mar 7, 1997·The Journal of Biological Chemistry·S A CoolicanJ R Florini
Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·K MurataD L Brautigan
Jul 2, 1998·Biochemical and Biophysical Research Communications·J ChenS L Schreiber
Oct 17, 1998·Molecular Cell·H NishitohH Ichijo
Nov 6, 1998·Molecular Pharmacology·H HosoiP J Houghton
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·R T PetersonS L Schreiber
Oct 12, 1999·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·G L Blatch, M Lässle
Dec 28, 1999·Proceedings of the National Academy of Sciences of the United States of America·J S HardwickS L Schreiber
Jan 4, 2001·Trends in Endocrinology and Metabolism : TEM·M Chinkers
Apr 12, 2001·Genes & Development·A C GingrasN Sonenberg
Jun 20, 2001·Circulation·J SunL E Rabbani
Aug 14, 2001·The Journal of Biological Chemistry·E Erbay, J Chen
Nov 3, 2001·Science·P B DennisG Thomas
Feb 22, 2002·European Journal of Biochemistry·Shinri TamuraTakayasu Kobayashi
Apr 27, 2002·Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme·Shinri TamuraTakayasu Kobayashi
May 10, 2002·The Journal of Biological Chemistry·Xiongwen ZhangPeter J Houghton
Aug 9, 2002·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yoshihiko KonoNobuo Sakaguchi
Feb 4, 2003·Nature Reviews. Molecular Cell Biology·Estela Jacinto, Michael N Hall

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Citations

Dec 4, 2004·The EMBO Journal·Jing YangDavid Barford
Aug 14, 2008·The Journal of Biological Chemistry·Melissa PopowskiCarla L Van Den Berg
Sep 22, 2007·Annual Review of Pharmacology and Toxicology·Kohsuke TakedaHidenori Ichijo
Feb 9, 2012·Physiology·Haipeng Sun, Yibin Wang
May 30, 2009·The Journal of Clinical Investigation·Adam D DurbinDavid Malkin
Apr 26, 2011·Head & Neck Oncology·Yu-Min LiaoYun Yen
Apr 7, 2011·Experimental & Molecular Medicine·Chang Hoon Cho
Apr 1, 2014·The Journal of Endocrinology·Henrik OrtsäterÅke Sjöholm
Jun 7, 2006·Leukemia & Lymphoma·Yasuhiro MaedaAkihisa Kanamaru
Oct 4, 2006·Free Radical Research·Honglei LiuHenry Jay Forman
Apr 19, 2005·Expert Opinion on Investigational Drugs·Janet E Dancey
Aug 3, 2010·The International Journal of Biochemistry & Cell Biology·Mikhail A KutuzovAlexandra V Andreeva
Apr 29, 2009·Gastroentérologie Clinique Et Biologique·A HollebecqueS Dharancy
Mar 23, 2005·Current Opinion in Cell Biology·Monica Gallego, David M Virshup
Mar 29, 2014·Biological Reviews of the Cambridge Philosophical Society·Yuehua WeiMang-Hua Xu
Aug 21, 2014·Biochemical and Biophysical Research Communications·Pengpeng ZhangShihuan Kuang
Feb 4, 2011·Critical Reviews in Toxicology·Susana R PereiraAgostinho Antunes
Mar 23, 2015·Cellular and Molecular Neurobiology·Xinglong ZhiGuilin Li
Nov 10, 2012·Biochimica Et Biophysica Acta·Wim J van Blitterswijk, Marcel Verheij
Aug 1, 2012·Biochemical and Biophysical Research Communications·Maruf H KhanShane L Rea
Feb 19, 2008·Biochimica Et Biophysica Acta·Teresa GoldenRichard E Honkanen
Jul 12, 2016·Biochemical Pharmacology·Hongyu ZhouShile Huang

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