Apoptosis induction by activator protein 2alpha involves transcriptional repression of Bcl-2

The Journal of Biological Chemistry
Narendra WajapeyeeKumaravel Somasundaram

Abstract

Activator protein 2alpha (AP-2alpha) induces cytotoxicity by inducing cell cycle arrest and apoptosis. In this study we investigated the mechanism of apoptosis induction by AP-2alpha. We found that AP-2alpha induced apoptosis efficiently in cells treated with benzyloxycar-bonyl-IETD-fluoromethyl ketone or FADD-silenced cells but failed to do so in benzyloxycarbonyl-LEHD-fluoromethyl ketone-treated or apoptosis protease activation factor-1 (Apaf1)-silenced cells, suggesting the central role of mitochondria in AP-2alpha-induced apoptosis. In good correlation, cells overexpressing AP-2alpha showed a reduction in mitochondrial membrane potential (Deltapsi(m)), cytochrome c and Smac/DIABLO release into cytosol, and Bax translocation into mitochondria. We found that the pro-apoptotic protein Bax is important for AP-2alpha-induced apoptosis as adenovirus AP2 failed to induce apoptosis in HCT116 Bax(-/-) cells. However, we found the IAP (inhibitor of apoptosis) inhibitor Smac/DIABLO may have a limited role in AP-2alpha-induced apoptosis as we found the IAP member Survivin down-regulated by AP-2alpha. Although the total Bax level remains unaltered, we found a time-dependent increase in the activated form of Bax in adenovirus AP2-infecte...Continue Reading

References

Mar 1, 1991·Trends in Genetics : TIG·C J Marshall
Apr 2, 1996·Proceedings of the National Academy of Sciences of the United States of America·K SomasundaramB Thimmapaya
Jan 1, 1997·Nature Genetics·Y X ZengW S el-Deiry
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
Nov 13, 1998·Proceedings of the National Academy of Sciences of the United States of America·T NottoliT Williams
Nov 17, 1998·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J M KarjalainenV M Kosma
May 14, 1999·Trends in Biochemical Sciences·T A MillwardB A Hemmings
Dec 28, 1999·Annual Review of Cell and Developmental Biology·I BudihardjoX Wang
Jun 23, 2000·British Journal of Cancer·M A AnttilaV M Kosma
Jul 19, 2000·The Journal of Biological Chemistry·S WankhadeP Kannan
Sep 1, 2000·Journal of Molecular Biology·M A GarcíaJ Vázquez
Nov 4, 2000·Science·L ZhangB Vogelstein
Sep 13, 2002·The Journal of Biological Chemistry·Lisa A McPhersonRonald J Weigel
Nov 5, 2003·Journal of Cellular and Molecular Medicine·Alexandrina Burlacu
Apr 17, 2004·Cancer Research·Bo LuDennis E Hallahan
Aug 3, 2004·Science·Douglas R Green, Guido Kroemer
Feb 24, 2005·Cancer Biology & Therapy·Zhaoyu Jin, Wafik S El-Deiry
Mar 5, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Amy B HeimbergerKenneth Aldape

❮ Previous
Next ❯

Citations

Aug 14, 2012·Journal of Molecular Histology·Ling ZhangZhan Zhang
Jan 17, 2013·Journal of Medicinal Chemistry·Duraippandi PalanimuthuAshoka G Samuelson
Oct 11, 2008·Cancer Gene Therapy·B A Guinn, R Mulherkar
Feb 2, 2013·Genetic Testing and Molecular Biomarkers·Solmaz Moniri JavadhesariMonireh Halimi
Mar 8, 2011·Breast Cancer Research : BCR·Chiara BerlatoHelen C Hurst
May 22, 2013·PloS One·Soumya Alige Mahabala RaoKumaravel Somasundaram
Apr 8, 2011·World Journal of Gastroenterology : WJG·Anastasia PavlidouKleanthi Dimas
Aug 8, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Nand K Sah, Chandrabhan Seniya
Sep 9, 2015·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Rupa MishraTanuja Teni
Oct 30, 2007·Journal of Dermatological Science·Priyadharsini Nagarajan, Satrajit Sinha
Jan 29, 2016·In Silico Pharmacology·Padmaa M PaarakhSujan P S Ganapathy
Apr 30, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Francesca OrsoDaniela Taverna
Jun 12, 2019·Molecular and Cellular Biology·Jiuling WangYandong Zhang
Jan 20, 2016·International Journal of Oncology·Wenhuan HuangJian Zhang
Jul 23, 2014·International Journal of Molecular Medicine·Xiangjun MengLili Jia
Dec 29, 2009·Molecular and Cellular Endocrinology·Stuart Handwerger

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

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