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

  1. Deepak Nijhawan1,
  2. Min Fang1,
  3. Elie Traer,
  4. Qing Zhong,
  5. Wenhua Gao,
  6. Fenghe Du, and
  7. Xiaodong Wang2
  1. Howard Hughes Medical Institute & Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA

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

Footnotes

  • Corresponding author.

  • 1 These authors contributed equally to this work.

  • 2 E-MAIL xwang{at}biochem.swmed.edu; FAX (214) 648-9729.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1093903.

    • Accepted April 18, 2003.
    • Received March 17, 2003.
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