Abstract
Bax, a member of the Bcl-2 family of proteins, has been shown to accelerate apoptosis induced by growth factor withdrawal, gamma-irradiation, and the chemotherapeutic agent, etoposide. The mechanism by which Bax promotes apoptosis is poorly understood. Bax forms homodimers which have been suggested to act as accelerators or inducers of cell death. However, the requirement for homodimerization of Bax to promote cell death remains unclear. We performed site-directed mutagenesis of the BH1, BH2, and BH3 in Bax to determine the regions of Bax required for homodimerization and to define the role of Bax homodimers in cell death induced by chemotherapy drugs. Bax proteins expressing alanine substitutions of the highly conserved amino acids glycine 108 (G108) in BH1, tryptophan 158 (W158) in BH2, and glycine 67 and aspartic acid 68 (GD67-68) in BH3 as well as deletion of the most conserved amino acids in BH1 (Delta102-112) and BH2 (Delta151-159) and deletion of BH3 (Delta63-71) maintained their ability to accelerate chemotherapy-induced cell death. Immunoprecipitation studies revealed that Bax with deletions in BH1 and BH2 still associated with wild-type Bax while deletion of BH3 disrupted Bax homodimerization. These results demonstrat...Continue Reading
References
Apr 2, 1992·Nature·M C Raff
Jun 3, 1991·Journal of Immunological Methods·I NicolettiC Riccardi
Sep 29, 1988·Nature·D L VauxJ M Adams
Oct 6, 1995·Science·C M KnudsonS J Korsmeyer
Feb 1, 1995·Critical Reviews in Oncology/hematology·S J Martin, D R Green
Jan 27, 1995·Cell·E YangS J Korsmeyer
Mar 10, 1995·Science·C B Thompson
Oct 21, 1994·Cell·Z N Oltvai, S J Korsmeyer
Aug 26, 1994·Cell·D E Fisher
Sep 10, 1993·Cell·G T Williams, C A Smith
May 26, 1994·Nature·X M YinS J Korsmeyer
Aug 27, 1993·Cell·Z N OltvaiS J Korsmeyer
Jan 1, 1996·Genes & Development·E White
Feb 8, 1996·Nature·E H ChengJ M Hardwick
Apr 12, 1996·The Journal of Biological Chemistry·J J Hunter, T G Parslow
Mar 15, 1996·The Journal of Biological Chemistry·A J MinnC B Thompson
Mar 29, 1996·The Journal of Biological Chemistry·H ZhaJ C Reed
Sep 13, 1996·The Journal of Biological Chemistry·P L SimonianG Nuñez
Nov 1, 1994·Trends in Cell Biology·G Nuñez, M F Clarke
Citations
Jul 29, 1998·International Journal of Cancer. Journal International Du Cancer·U Naumann, M Weller
Dec 21, 2002·Molecular Immunology·Christoph Borner
Aug 28, 2001·British Journal of Pharmacology·H Z Lee
Nov 25, 2000·British Journal of Haematology·D A Fennell, F E Cotter
Sep 29, 2006·The Journal of Biological Chemistry·Jun PengJialing Lin
Jun 12, 1999·Thyroid : Official Journal of the American Thyroid Association·F Labat-MoleurA Negoescu
Jul 22, 1998·The EMBO Journal·A GrossS J Korsmeyer
Apr 4, 2000·The EMBO Journal·S ConusC Borner
Nov 18, 1997·European Journal of Biochemistry·M SimonenJ Heim
May 24, 2007·BMC Cell Biology·Neha ParikhApurva Sarin
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·J Pawlowski, A S Kraft
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·P De FeudisM Broggini
Mar 5, 2004·Biochimica Et Biophysica Acta·Vladimir KirkinMartin Zörnig
May 13, 2008·Molecular Cell·Grant DewsonRuth M Kluck
Nov 18, 1998·Japanese Journal of Cancer Research : Gann·E TashiroM Imoto
Dec 21, 2000·Japanese Journal of Cancer Research : Gann·A Salah-eldinA Matsuura
May 30, 1998·The Journal of Biological Chemistry·Y T Hsu, R J Youle
Feb 1, 2011·Journal of Gynecologic Oncology·Ke Long JinJoo-Hyun Nam
Apr 13, 2006·The Journal of Biological Chemistry·Lihua MingLin Zhang
Apr 29, 1998·Immunology and Cell Biology·L F Lincz
Nov 7, 1998·The Journal of Biological Chemistry·S Y Hsu, A J Hsueh
Jun 20, 1998·The Journal of Biological Chemistry·M YasudaG Chinnadurai
Feb 12, 1998·The Journal of Biological Chemistry·H Zha, J C Reed
Sep 19, 1998·Molecular and Cellular Biology·K WangS J Korsmeyer
Dec 20, 2002·Transplantation·Dolca ThomasManikkam Suthanthiran
Jun 9, 2007·The Journal of Biological Chemistry·Emine ErFrançois M Vallette
Feb 12, 1998·Biochemical and Biophysical Research Communications·J D RobertsonJ P Kehrer
Mar 2, 1999·Biochemical and Biophysical Research Communications·Y J TanA E Ting