ArticleCell death & disease2010
Phosphorylation of Puma modulates its apoptotic function by regulating protein stability.
Article in Cell death & disease, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Review
- Review
- The multifaceted role of PUMA in cell death pathways: its therapeutic potential across cancer types.Cell communication and signaling : CCS · 2025Review
- The Role of Vitamin D in Gastrointestinal Homeostasis and Gut Inflammation.International journal of molecular sciences · 2025Review
- Intracellular BAPTA directly inhibits PFKFB3, thereby impeding mTORC1-driven Mcl-1 translation and killing MCL-1-addicted cancer cells.Cell death & disease · 2023Article
- BCL-2 protein family: attractive targets for cancer therapy.Apoptosis : an international journal on programmed cell death · 2023Review
- BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis.Life (Basel, Switzerland) · 2022Review
- Article
- Article
- MiR-35 buffers apoptosis thresholds in the C. elegans germline by antagonizing both MAPK and core apoptosis pathways.Cell death and differentiation · 2019Article
- Selective and Apoptotic Action of Ethanol Extract of Annona cherimola Seeds against Human Stomach Gastric Adenocarcinoma Cell Line AGS.Plant foods for human nutrition (Dordrecht, Netherlands) · 2019Article
- Article
- The impact of phosphatases on proliferative and survival signaling in cancer.Cellular and molecular life sciences : CMLS · 2018Review
- Neuronal Cell Death.Physiological reviews · 2018Review
- Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer.eLife · 2016Article
- Loss of the Ubiquitin-conjugating Enzyme UBE2W Results in Susceptibility to Early Postnatal Lethality and Defects in Skin, Immune, and Male Reproductive Systems.The Journal of biological chemistry · 2016Article
- Subcellular localization of PUMA regulates its pro-apoptotic activity in Burkitt's lymphoma B cells.Oncotarget · 2015Article
- The BH3-only protein Bad is dispensable for TNF-mediated cell death.Cell death & disease · 2015Article
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- Article
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Authors and funding
4 authors.
Funding
Abstract
Puma is a potent BH3-only protein that antagonises anti-apoptotic Bcl-2 proteins, promotes Bax/Bak activation and has an essential role in multiple apoptotic models. Puma expression is normally kept very low, but can be induced by several transcription factors including p53, p73, E2F1 and FOXO3a, whereby it can induce an apoptotic response. As Puma can to bind and inactivate all anti-apoptotic members of the Bcl-2 family, its activity must be tightly controlled. We report here, for the first time, evidence that Puma is subject to post-translational control through phosphorylation. We show that Puma is phosphorylated at multiple sites, with the major site of phosphorylation being serine 10. Replacing serine 10 with alanine causes reduced Puma turnover and enhanced cell death. Interestingly, Puma turnover occurs through the proteasome, and substitution of serine 10 causes elevated Puma levels independently of macroautophagy, Bcl-2 family member binding, caspase activity and apoptotic death. We conclude, therefore, that phosphorylation of Puma at serine 10 promotes Puma turnover, represses Puma's cell death potential and promotes cell survival. Owing to the highly pro-apoptotic nature of Puma, these studies highlight an important additional regulatory step in the determination of cellular life or death.
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