PubAg

Main content area

Phosphorylation alters Bim‐mediated Mcl‐1 stabilization and priming

Author:
Conage‐Pough, Jason E., Boise, Lawrence H.
Source:
TheFEBS journal 2018 v.285 no.14 pp. 2626-2640
ISSN:
1742-464X
Subject:
apoptosis, mutation, phosphorylation, proteins
Abstract:
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.