Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation

Deepak Nijhawan, Min Fang, Elie Traer, Qing Zhong, Wenhua Gao, Fenghe Du, Xiaodong Wang

Research output: Contribution to journalArticlepeer-review

484 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1475-1486
Number of pages12
JournalGenes and Development
Volume17
Issue number12
DOIs
StatePublished - Jun 15 2003

Keywords

  • Apoptosis
  • Bcl-x
  • Cytochrome c
  • Mcl-1
  • Mitochondria
  • Proteasome

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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