ArticleCell death & disease2021
Phosphatase PP2A enhances MCL-1 protein half-life in multiple myeloma cells.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Spatiotemporal dynamics of Mcl-1 abundance and its influence on apoptosis susceptibility.bioRxiv : the preprint server for biology · 2026Article
- FGFR signaling and apoptotic regulation in cancer: links to immune evasion, therapeutic resistance, and treatment re-engagement.Frontiers in immunology · 2026Review
- Targeting MCL-1 to Overcome Therapeutic Resistance and Improve Cancer Mortality.Health science reports · 2025Article
- Construction of LncRNA-miRNA-mRNA regulatory network in IgA nephropathy mice model by RNA-sequencing and bioinformatics analysis.Genes & genomics · 2025Article
- Exploring BCL2 regulation and upstream signaling transduction in venetoclax resistance in multiple myeloma: potential avenues for therapeutic intervention.Blood cancer journal · 2025Article
- Kinase signalling adaptation supports dysfunctional mitochondria in disease.Frontiers in molecular biosciences · 2024Review
- Mitoribosomal synthetic lethality overcomes multidrug resistance in MYC-driven neuroblastoma.Cell death & disease · 2023Article
- The TT Genotype of theCells · 2023Article
- Proteasome Inhibitors Silence Oncogenes in Multiple Myeloma through Localized Histone Deacetylase 3 (HDAC3) Stabilization and Chromatin Condensation.Cancer research communications · 2022Article
- Understanding MCL1: from cellular function and regulation to pharmacological inhibition.The FEBS journal · 2022Review
- Patent landscape of inhibitors and PROTACs of the anti-apoptotic BCL-2 family proteins.Expert opinion on therapeutic patents · 2022Review
- Over Fifty Years of Life, Death, and Cannibalism: A Historical Recollection of Apoptosis and Autophagy.International journal of molecular sciences · 2021Review
- Interplay between protein acetylation and ubiquitination controls MCL1 protein stability.Cell reports · 2021Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple myeloma (MM), a treatable but incurable malignancy, is characterized by the growth of clonal plasma cells in protective niches in the bone marrow. MM cells depend on expression of BCL-2 family proteins, in particular MCL-1, for survival. The regulation of MCL-1 is complex and cell type-dependent. Unraveling the exact mechanism by which MCL-1 is overexpressed in MM may provide new therapeutic strategies for inhibition in malignant cells, preferably limiting side effects in healthy cells. In this study, we reveal that one cause of overexpression could be stabilization of the MCL-1 protein. We demonstrate this in a subset of MM and diffuse large B cell lymphoma (DLBCL) cell lines and MM patient samples. We applied a phosphatase siRNA screen to identify phosphatases responsible for MCL-1 stabilization in MM, and revealed PP2A as the MCL-1 stabilizing phosphatase. Using the PP2A inhibitor okadaic acid, we validated that PP2A dephosphorylates MCL-1 at Ser159 and/or Thr163, and thereby stabilizes MCL-1 in MM cells with long MCL-1 half-life, but not in DLBCL cells. Combined kinase and phosphatase inhibition experiments suggest that the MCL-1 half-life in MM is regulated by the counteracting functions of JNK and PP2A. These findings increase the understanding of the mechanisms by which MCL-1 is post-translationally regulated, which may provide novel strategies to inhibit MCL-1 in MM cells.
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