How the Bcl-2 family of proteins interact to regulate apoptosis

被引:284
|
作者
van Delft, MF
Huang, DC
机构
[1] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia
[2] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia
关键词
apoptosis; cell death; Bcl-2; Mcl-1; BH3; mimetic;
D O I
10.1038/sj.cr.7310028
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Commitment of cells to apoptosis is governed largely by protein-protein interactions between members of the Bcl-2 protein family. Its three sub-families have distinct roles: the BH3-only proteins trigger apoptosis by binding via their BH3 domain to pro-survival relatives, while the pro-apoptotic Bax and Bak have an essential downstream role involving disruption of organellar membranes and induction of caspase activation. The BH3-only proteins act as damage sensors, held inert until their activation by stress signals. Once activated, they were thought to bind promiscuously to pro-survival protein targets but unexpected selectivity has recently emerged from analysis of their interactions. Some BH3-only proteins also bind to Bax and Bak. Whether Bax and Bak are activated directly by these BH3-only proteins, or indirectly as a consequence of BH3-only proteins neutralizing their pro-survival targets is the subject of intense debate. Regardless of this, a detailed understanding of the interactions between family members, which are often selective, has notable implications for designing anti-cancer drugs to target the Bcl-2 family.
引用
收藏
页码:203 / 213
页数:11
相关论文
共 50 条
  • [41] Apoptosis in nontumorous and neoplastic human pituitaries - Expression of the Bcl-2 family of proteins
    Kulig, E
    Jin, L
    Qian, X
    Horvath, E
    Kovacs, K
    Stefaneanu, L
    Scheithauer, BW
    Lloyd, RV
    AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (03): : 767 - 774
  • [42] The control of endoplasmic reticulum-initiated apoptosis by the BCL-2 family of proteins
    Oakes, SA
    Lin, SS
    Bassik, MC
    CURRENT MOLECULAR MEDICINE, 2006, 6 (01) : 99 - 109
  • [43] Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis
    Oldereid, NB
    De Angelis, P
    Wiger, R
    Clausen, OPF
    MOLECULAR HUMAN REPRODUCTION, 2001, 7 (05) : 403 - 408
  • [44] Permeabilisation of mitochondrial outer membrane by Bcl-2 family proteins during apoptosis
    Kuwana, T
    Newmeyer, DD
    MOLECULAR BIOLOGY OF THE CELL, 2002, 13 : 146A - 146A
  • [45] Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins
    Singh, Rumani
    Letai, Anthony
    Sarosiek, Kristopher
    NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2019, 20 (03) : 175 - 193
  • [46] Role for the Bcl-2 family proteins and BH3 domain in apoptosis
    Liu, XJ
    Zhang, LQ
    Liu, XL
    He, FC
    PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS, 2006, 33 (03) : 221 - 225
  • [47] Modulation of Bcl-2 family proteins in primary endothelial cells during apoptosis
    Molostvov, G
    Morris, A
    Rose, P
    Basu, S
    PATHOPHYSIOLOGY OF HAEMOSTASIS AND THROMBOSIS, 2002, 32 (02) : 85 - 91
  • [48] Apoptosis and Bcl-2 family proteins, taken to chronic obstructive pulmonary disease
    Zeng, Huihui
    Kong, Xianglong
    Peng, Hong
    Chen, Yan
    Cai, Shan
    Luo, Hong
    Chen, Ping
    EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2012, 16 (06) : 711 - 727
  • [49] Control of apoptosis by using small molecule regulators of Bcl-2 family proteins
    Wang, JL
    Zhang, ZJ
    Choksi, S
    Shan, SM
    Lu, ZX
    Croce, CM
    Alnemri, ES
    Korngold, R
    Huang, ZW
    PEPTIDES FOR THE NEW MILLENNIUM, 2000, : 217 - 218
  • [50] Essential roles of the Bcl-2 family of proteins in caspase-2-induced apoptosis
    Gao, ZH
    Shao, YF
    Jiang, XJ
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (46) : 38271 - 38275