Phosphorylation alters Bim‐mediated Mcl‐1 stabilization and priming
Open accessAbstract
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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Phosphorylated BIM binds to and stabilizes MCL-1.
“As a possible mechanism for this observation, it has been previously reported that phosphorylated BIM binds to and stabilizes MCL-130.”
From Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer (2024) · cites this paper as [30]
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Combined inhibition of KRASG12C and mTORC1 kinase is synergistic in non-small cell lung cancer
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“As a possible mechanism for this observation, it has been previously reported that phosphorylated BIM binds to and stabilizes MCL-1 30 .”
Background
- 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
- PMC
- PMC6215700
- 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
- bronze
- doi.org
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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