Cdk2 phosphorylation of Bcl-xL after stress converts it to a pro-apoptotic protein mimicking Bax/Bak
| Autor: | Adel Tarcsafalvi, Nshl Seng, Peter M. Price, Rawad Hodeify, Judit Megyesi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death Cytochrome c Immunology Bcl-2 family Bcl-xL Cell Biology Biology Mitochondrial apoptosis-induced channel Article Cell biology 03 medical and health sciences Cellular and Molecular Neuroscience 030104 developmental biology Apoptosis biology.protein Phosphorylation Inner mitochondrial membrane |
| Zdroj: | Cell Death Discovery |
| ISSN: | 2058-7716 |
| DOI: | 10.1038/cddiscovery.2015.66 |
| Popis: | Apoptosis is a regulated form of cell death that proceeds by defined biochemical pathways. Most apoptosis is controlled by interactions between pro-survival and pro-apoptotic Bcl-2 family proteins in which death is often the consequence of permeabilization of the mitochondrial outer membrane. Many drugs affect this equilibrium to favor apoptosis but this process is not completely understood. We show that the chemotherapeutic drug cisplatin initiates an apoptotic pathway by phosphorylation of a pro-survival Bcl-2 family member, Bcl-xL, by cyclin-dependent kinase 2. The phosphorylation occurred at a previously unreported site and its biologic significance was demonstrated by a phosphomimetic modification of Bcl-xL that was able to induce apoptosis without addition of cisplatin. The mechanism of cell death induction was similar to that initiated by pro-apoptotic Bcl-2 family proteins, that is, phosphorylated Bcl-xL translocated to the mitochondrial membrane, and formed pores in the membrane. This initiated cytochrome c release and caspase activation that resulted in cell death. |
| Databáze: | OpenAIRE |
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