BH3-only proteins in apoptosis and beyond: an overview

被引：0
作者：
E Lomonosova
G Chinnadurai
机构：
[1] Institute for Molecular Virology,
[2] Saint Louis University School of Medicine,undefined
[3] Doisy Research Center,undefined
[4] 2Current address: Department of Molecular Microbiology and Immunology,undefined
[5] Saint Louis University School of Medicine,undefined
来源：
Oncogene | 2008年 / 27卷
关键词：
BH3-only; apoptosis; autophagy; non-apoptotic functions; cancer;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
BH3-only BCL-2 family proteins are effectors of canonical mitochondrial apoptosis. They discharge their pro-apoptotic functions through BH1–3 pro-apoptotic proteins such as BAX and BAK, while their activity is suppressed by BH1–4 anti-apoptotic BCL-2 family members. The precise mechanism by which BH3-only proteins mediate apoptosis remains unresolved. The existing data are consistent with three mutually non-exclusive models (1) displacement of BH1–3 proteins from complexes with BH1–4 proteins; (2) direct interaction with and conformational activation of BH1–3 proteins; and (3) membrane insertion and membrane remodeling. The BH3-only proteins appear to play critical roles in restraining cancer and inflammatory diseases such as rheumatoid arthritis. Molecules that mimic the effect of BH3-only proteins are being used in treatments against these diseases. The cell death activity of a subclass of BH3-only members (BNIP3 and BNIP3L) is linked to cardiomyocyte loss during heart failure. In addition to their established role in apoptosis, several BH3-only members also regulate diverse cellular functions in cell-cycle regulation, DNA repair and metabolism. Several members are implicated in the induction of autophagy and autophagic cell death, possibly through unleashing of the BH3-only autophagic effector Beclin 1 from complexes with BCL-2/BCL-xL. The Chapters included in the current Oncogene Review issues provide in-depth discussions on various aspects of major BH3-only proteins.
引用
收藏
页码：S2 / S19
相关论文
共 1118 条
[1]  
Akiyama T(2003)Regulation of osteoclast apoptosis by ubiquitylation of proapoptotic BH3-only Bcl-2 family member Bim EMBO J 22 6653-6664
[2]  
Bouillet P(2003)Mutations of the BIK gene in human peripheral B-cell lymphomas Genes Chromosomes Cancer 38 91-96
[3]  
Miyazaki T(2005)Dexamethasone resistance in B-cell precursor childhood acute lymphoblastic leukemia occurs downstream of ligand-induced nuclear translocation of the glucocorticoid receptor Blood 105 2519-2526
[4]  
Kadono Y(2000)MCL-1S, a splicing variant of the antiapoptotic BCL-2 family member MCL-1, encodes a proapoptotic protein possessing only the BH3 domain J Biol Chem 275 25255-25261
[5]  
Chikuda H(2005)Deletion of Bid impedes cell proliferation and hepatic carcinogenesis Am J Pathol 166 1523-1532
[6]  
Chung UI(2005)The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death Mol Cell 18 637-650
[7]  
Arena V(2000)Human DNA damage checkpoint protein hRAD9 is a 3′–5′ exonuclease J Biol Chem 275 7451-7454
[8]  
Martini M(2000)Exon skipping in Mcl-1 results in a bcl-2 homology domain 3 only gene product that promotes cell death J Biol Chem 275 22136-22146
[9]  
Luongo M(2006)PKC regulates a farnesyl-electrostatic switch on K-Ras that promotes its association with Bcl-XL on mitochondria and induces apoptosis Mol Cell 21 481-493
[10]  
Capelli A(1999)Proapoptotic Bcl-2 relative Bim required for certain apoptotic responses, leukocyte homeostasis, and to preclude autoimmunity Science 286 1735-1738
12345678910