TBC1D3, a hominoid-specific gene, delays IRS-1 degradation and promotes insulin signaling by modulating p70 S6 kinase activity.

PloS One
Marisa J WainszelbaumPhilip D Stahl

Abstract

Insulin/IGF-1 signaling plays a pivotal role in the regulation of cellular homeostasis through its control of glucose metabolism as well as due to its effects on cell proliferation. Aberrant regulation of insulin signaling has been repeatedly implicated in uncontrolled cell growth and malignant transformations. TBC1D3 is a hominoid specific gene previously identified as an oncogene in breast and prostate cancers. Our efforts to identify the molecular mechanisms of TBC1D3-induced oncogenesis revealed the role of TBC1D3 in insulin/IGF-1 signaling pathway. We document here that TBC1D3 intensifies insulin/IGF-1-induced signal transduction through intricate, yet elegant fine-tuning of signaling mechanisms. We show that TBC1D3 expression substantially delayed ubiquitination and degradation of insulin receptor substrate-1 (IRS-1). This effect is achieved through suppression of serine phosphorylation at S636/639, S307 and S312 of IRS-1, which are key phosphorylation sites required for IRS-1 degradation. Furthermore, we report that the effect of TBC1D3 on IRS-1:S636/639 phosphorylation is mediated through TBC1D3-induced activation of protein phosphatase 2A (PP2A), followed by suppression of T389 phosphorylation on p70 S6 kinase (S6K). T...Continue Reading

References

Jan 1, 1991·Methods in Enzymology·D G HardieA T Sim
Dec 1, 1993·Molecular and Cellular Biology·X J SunM F White
May 1, 1993·Cell Adhesion and Communication·Y van KooykC G Figdor
Jan 1, 1995·Progress in Cell Cycle Research·R B Pearson, G Thomas
Apr 25, 2000·The Journal of Biological Chemistry·C A MolloyB R Westley
May 12, 2001·Mechanisms of Ageing and Development·G L Boulianne
Jun 28, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·L ZhuB J Goldstein
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Charles A PauldingDaniel A Haber
Mar 17, 2004·Biochemical and Biophysical Research Communications·Christian J CarlsonCristina M Rondinone
Jul 14, 2004·The Journal of Cell Biology·Laura S HarringtonRichard F Lamb
Jan 7, 2005·Swiss Medical Weekly·E Hafen
Jan 18, 2005·Trends in Biochemical Sciences·Laura S HarringtonRichard F Lamb
Jan 27, 2005·Science's STKE : Signal Transduction Knowledge Environment·Yehiel Zick
Mar 1, 2005·Biochimie·Philippe GualJean-François Tanti
Feb 24, 2006·Nature Reviews. Molecular Cell Biology·Cullen M TaniguchiC Ronald Kahn
Jun 16, 2007·Experimental Cell Research·Vincent A Bielinski, Marc C Mumby
Jul 5, 2007·PLoS Biology·Uhn Soo ChoWenqing Xu
Nov 9, 2007·Annual Review of Physiology·Akiko Taguchi, Morris F White
Nov 28, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michele ClampEric S Lander
Jan 18, 2008·Molecular Biology of the Cell·Emanuela FrittoliStefano Confalonieri
Mar 6, 2008·The Journal of Biological Chemistry·Marisa J WainszelbaumPhilip D Stahl
Aug 30, 2008·American Journal of Physiology. Endocrinology and Metabolism·Sigalit Boura-Halfon, Yehiel Zick
Sep 9, 2008·Genome Research·George H PerryRichard Redon
Mar 3, 2009·Vitamins and Hormones·Xiao Jian Sun, Feng Liu
Oct 13, 2009·Molecular Cell·Mei KongCraig B Thompson
May 7, 2010·Cell Metabolism·Katrin HahnAurelio A Teleman

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Citations

Aug 21, 2013·Nature Reviews. Genetics·Sidi ChenManyuan Long
Jul 17, 2015·International Journal of Molecular Medicine·Julian Banerji
Nov 14, 2013·Cellular Signalling·Florian ScheufeleAntonio Sarikas
Feb 26, 2016·Critical Reviews in Biochemistry and Molecular Biology·Nathan Wlodarchak, Yongna Xing
Apr 13, 2013·Biochemical and Biophysical Research Communications·Chen KongPhilip D Stahl
Feb 5, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shu QinBrian P Eliceiri
Sep 25, 2016·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Andrew BairdBrian P Eliceiri
Nov 19, 2015·Annals of Surgical Oncology·Akiko HanyudaShuji Ogino
Jul 5, 2013·Cell Metabolism·Josefine LindroosMartin Bilban

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Methods Mentioned

BETA
ubiquitination
PCR
co-immunoprecipitation
immunoprecipitation
Assay

Software Mentioned

AlphaEaseFc

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