Phosphorylation alters Bim-mediated Mcl-1 stabilization and priming

被引：19

作者：

Conage-Pough, Jason E. ^{[1
,2
]}

Boise, Lawrence H. ^{[2
]}

机构：

[1] Emory Univ, Canc Biol Grad Program, Winship Canc Inst, Atlanta, GA 30322 USA

[2] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA 30322 USA

来源：

FEBS JOURNAL | 2018年 / 285卷 / 14期

关键词：

Bim phosphorylation; Mcl-1; stability; priming; MITOCHONDRIAL-MEMBRANE PERMEABILIZATION; BREAST-CANCER CELLS; BCL-2; FAMILY; INDUCED APOPTOSIS; BH3; DOMAINS; WALDENSTROM MACROGLOBULINEMIA; BIM(EL) PHOSPHORYLATION; PROAPOPTOTIC ACTIVITY; BH3-ONLY LIGANDS; OLIGOMERIZES BAK;

D O I：

10.1111/febs.14505

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：

Mcl-1 is a highly labile protein, subject to extensive post-translational regulation. This distinguishes Mcl-1 from other antiapoptotic proteins and necessitates further study to better understand how interactions with proapoptotic Bcl-2 proteins affect its regulation. One such protein, Bim, is known to stabilize Mcl-1, and Bim phosphorylation has been associated with increased Mcl-1 binding. Consequently, we investigated the potential impact of Bim phosphorylation on Mcl-1 stability. We found that Bim stabilizes and primes Mcl-1 in RPCI-WM1 cells and is constitutively phosphorylated. Additionally, introduction of several phospho-mimetic and unphosphosphorylateable Bim mutations resulted in altered Mcl-1 stability and distinct Bim binding to antiapoptotic proteins. These findings suggest Bim phosphorylation not only regulates Mcl-1 stability but also is a potential mechanism for enforcing Mcl-1 dependence.

引用

页码：2626 / 2640

页数：15

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