Anti-apoptotic proteins BCL-2, MCL-1 and A1 summate collectively to maintain survival of immune cell populations both in vitro and in vivo

被引：113

作者：

Carrington, Emma M. ^{[1
,2
]}

Zhan, Yifan ^{[1
,2
]}

Brady, Jamie L. ^{[1
,2
]}

Zhang, Jian-Guo ^{[1
,2
]}

Sutherland, Robyn M. ^{[1
,2
]}

Anstee, Natasha S. ^{[1
,2
]}

Schenk, Robyn L. ^{[1
,2
]}

Vikstrom, Ingela B. ^{[1
]}

Delconte, Rebecca B. ^{[1
,2
]}

Segal, David ^{[1
,2
]}

Huntington, Nicholas D. ^{[1
,2
]}

Bouillet, Philippe ^{[1
,2
]}

Tarlinton, David M. ^{[1
,2
,3
]}

Huang, David C. S. ^{[1
,2
]}

Strasser, Andreas ^{[1
,2
]}

Cory, Suzanne ^{[1
,2
]}

Herold, Marco J. ^{[1
,2
]}

Lew, Andrew M. ^{[1
,2
,4
]}

机构：

[1] Walter & Eliza Hall Inst Med Res, 1G Royal Parade, Parkville, Vic 3052, Australia

[2] Univ Melbourne, Dept Med Biol, Parkville, Vic 3010, Australia

[3] Monash Univ, Dept Immunol & Pathol, Melbourne, Vic 3004, Australia

[4] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia

来源：

CELL DEATH AND DIFFERENTIATION | 2017年 / 24卷 / 05期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

CHRONIC LYMPHOCYTIC-LEUKEMIA; BH3-ONLY PROTEINS; IMMUNOHISTOCHEMICAL ANALYSIS; HEMATOPOIETIC COMPARTMENT; MITOCHONDRIAL-MEMBRANE; MULTIPLE-MYELOMA; BH3; DOMAINS; EXPRESSION; INHIBITOR; ACTIVATION;

D O I：

10.1038/cdd.2017.30

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Survival of various immune cell populations has been proposed to preferentially rely on a particular anti-apoptotic BCL-2 family member, for example, naive T cells require BCL-2, while regulatory T cells require MCL-1. Here we examined the survival requirements of multiple immune cell subsets in vitro and in vivo, using both genetic and pharmacological approaches. Our findings support a model in which survival is determined by quantitative participation of multiple anti-apoptotic proteins rather than by a single anti-apoptotic protein. This model provides both an insight into how the sum of relative levels of anti-apoptotic proteins BCL-2, MCL-1 and A1 influence survival of T cells, B cells and dendritic cells, and a framework for ascertaining how these different immune cells can be optimally targeted in treatment of immunopathology, transplantation rejection or hematological cancers.

引用

页码：878 / 888

页数：11

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