Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation
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Open Access
- 3 June 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 17 (12) , 1475-1486
- https://doi.org/10.1101/gad.1093903
Abstract
Ultraviolet (UV) irradiation of HeLa cells triggers an apoptotic response mediated by mitochondria. Biochemical analysis of this response revealed that the elimination of cytosolic inhibitors is required for mitochondrial release of cytochrome c and subsequent caspase activation. These inhibitors were found to be Mcl-1 and Bcl-xL, two antiapoptotic members of the Bcl-2 family. Following UV treatment, Mcl-1 protein synthesis is blocked, the existing pool of Mcl-1 protein is rapidly degraded by the proteasome, and cytosolic Bcl-xL translocates to the mitochondria. These events are sequential; the elimination of Mcl-1 is required for the translocation of Bcl-xL. The disappearance of Mcl-1 is also required for other mitochondrial apoptotic events including Bax translocation, cytochrome c release, and caspase activation.Keywords
This publication has 51 references indexed in Scilit:
- Three-Dimensional Structure of the Apoptosome: Implications for Assembly, Procaspase-9 Binding, and ActivationPublished by Elsevier ,2002
- Apoptosis: A Link between Cancer Genetics and ChemotherapyPublished by Elsevier ,2002
- Identification of Omi/HtrA2 as a Mitochondrial Apoptotic Serine Protease That Disrupts Inhibitor of Apoptosis Protein-Caspase InteractionJournal of Biological Chemistry, 2002
- BH3-only proteins that bind pro-survival Bcl-2 family members fail to induce apoptosis in the absence of Bax and BakGenes & Development, 2001
- Proapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and DeathScience, 2001
- Identification of DIABLO, a Mammalian Protein that Promotes Apoptosis by Binding to and Antagonizing IAP ProteinsCell, 2000
- Smac, a Mitochondrial Protein that Promotes Cytochrome c–Dependent Caspase Activation by Eliminating IAP InhibitionCell, 2000
- The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of ApoptosisScience, 1997
- Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell deathCell, 1993
- Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cellsNature, 1988