Akt phosphorylates the TR3 orphan receptor and blocks its targeting to the mitochondria

Carcinogenesis
Hang-zi ChenQiao Wu

Abstract

Acutely transforming retrovirus AKT8 in rodent T cell lymphoma (Akt) phosphorylates and regulates the function of many cellular proteins involved in processes such as metabolism, apoptosis and proliferation. However, the precise mechanisms by which Akt promotes cell survival and inhibits apoptosis have been characterized in part only. TR3, an orphan receptor, functions as a transcription factor that can both positively or negatively regulate gene expression. We have reported previously that the translocation of TR3 from the nucleus to the mitochondria can elicit a proapoptotic effect in gastric cancer cells. In our present study, we demonstrate that Akt phosphorylates cytoplasmic TR3 through its physical interaction with the N-terminus of TR3. When coexpressed with Akt, TR3 mitochondrial targeting was blocked and this protein adopted a diffuse expression pattern in the cytoplasm. Moreover, Akt displayed an ability to disrupt the interaction of TR3 with Bcl-2, which is thought to be a critical requirement for mitochondrial TR3 to elicit apoptosis. Consistently, insulin was also found to induce the phosphorylation of TR3 and abolish 12-O-tetradecanoylphorbol-13-acetate-induced mitochondrial localization, which was dependent upon ...Continue Reading

References

Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·T G HazelL F Lau
Sep 15, 1988·Biochemical and Biophysical Research Communications·C Chang, J Kokontis
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·F WeihR Bravo
Apr 1, 1996·The Journal of Experimental Medicine·T ZhouJ D Mountz
Dec 31, 1997·The Journal of Biological Chemistry·R MeierB A Hemmings
Jul 11, 1998·The Journal of Biological Chemistry·M F FavataJ M Trzaskos
Nov 13, 1998·Science·M H CardoneJ C Reed
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·M ShtutmanA Ben-Ze'ev
Nov 11, 1999·European Journal of Immunology·A A KuangA Winoto
Jul 6, 2000·Nature Cell Biology·Y KatagiriG Guroff
Nov 4, 2000·The Journal of Cell Biology·H ZhouR N Pittman
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·Y PekarskyC M Croce
Jun 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·H K LinC Chang
Jul 5, 2001·The Journal of Biological Chemistry·N MasuyamaY Gotoh
Mar 8, 2002·Cellular Signalling·Karleen M Nicholson, Neil G Anderson
May 2, 2002·Cell·Astar Winoto, Dan R Littman
Jun 5, 2002·World Journal of Gastroenterology : WJG·Su LiuWen-Jin Su
Jul 11, 2002·The Journal of Biological Chemistry·Daniel C BerwickJeremy M Tavare
Jul 18, 2002·Endocrine-related Cancer·X-k Zhang
Nov 1, 2003·The International Journal of Biochemistry & Cell Biology·Xiao feng YeWen jin Su
Nov 13, 2003·Molecular and Cellular Biology·Siva Kumar KolluriXiao-kun Zhang
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley

❮ Previous
Next ❯

Citations

Sep 28, 2013·Cancer Immunology, Immunotherapy : CII·Shlomit Kfir-Erenfeld, Eitan Yefenof
Dec 3, 2014·Cellular Signalling·Jordan A BeardTaosheng Chen
May 5, 2009·Biochimica Et Biophysica Acta·Bernhard KadenbachSebastian Vogt
Mar 8, 2016·Gynecologic Oncology·Evan DelgadoSteffi Oesterreich
Oct 7, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lei ZhouHuiyan Zeng
May 11, 2013·The International Journal of Biochemistry & Cell Biology·Hang-zi ChenQiao Wu
Apr 28, 2012·Expert Opinion on Therapeutic Targets·Sally K Y ToAlice S T Wong
Dec 7, 2010·Biochimica Et Biophysica Acta·Liora LindenboimReuven Stein
Nov 30, 2011·Cancer Biology & Therapy·Shujing LiuXiaowei Xu
Jul 22, 2015·Molecular and Cellular Biology·Guijun YanJianxin Sun
Oct 19, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gengming NiuHuiyan Zeng
Jan 6, 2011·Expert Opinion on Therapeutic Targets·Syng-Ook LeeStephen Safe
Oct 3, 2018·Molecular Medicine Reports·Lingjuan Wu, Liqun Chen
Nov 11, 2018·The American Journal of Pathology·Asoka BannoRaju C Reddy

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis