Cited by 32Cell death mechanisms and regulationCancer-related Molecular PathwaysUbiquitin and proteasome pathways

Phosphorylation alters Bim‐mediated Mcl‐1 stabilization and priming

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Conage‐Pough, Jason E., Boise, Lawrence H.·2018·The FEBS Journal

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‐WM 1 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.

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Authors
Conage‐Pough, J. E., & Boise, L. H.
Affiliations
Emory University (US)
Corresponding author
Boise, Lawrence H.
Venue
The FEBS Journal
Publisher
Wiley
Published
2018-05-29
Volume
285
Issue
14
Pages
2626-2640
ISSN
  • 1742-464X (ISSN-L)
  • 1742-4658
OpenAlex
W2804123547
Cited by
32
References
77
Citations by year
2026: 5 · 2025: 7 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 1
FWCI
0.80
Type
journal article
Language
en
Open access
Locations
  • FEBS Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Cancer Institute (R01 CA192844)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
building information modeling, Mcl-1, protein phosphorylation, protein stability, Bcl-2 family proteins, apoptosis, anti-apoptotic proteins, protein-protein interaction
MeSH terms
Bortezomib, Bcl-2-Like Protein 11, Antineoplastic Agents, Humans, Mutation, Phosphorylation, Plasma Cells, Protein Binding, Protein Processing, Post-Translational, Signal Transduction, Gene Expression Regulation, Neoplastic, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Myeloid Cells, Cell Line, Tumor, bcl-X Protein, Protein Stability, HEK293 Cells, Myeloid Cell Leukemia Sequence 1 Protein

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