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The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis

Author

Listed:
  • Yuzuru Imai

    (Institute for Virus Research, Kyoto University)

  • Takaharu Kimura

    (Institute for Virus Research, Kyoto University)

  • Akira Murakami

    (Institute for Virus Research, Kyoto University)

  • Nobuyuki Yajima

    (Institute for Virus Research, Kyoto University)

  • Kazuhiro Sakamaki

    (Institute for Virus Research, Kyoto University)

  • Shin Yonehara

    (Institute for Virus Research, Kyoto University)

Abstract

Fas is a cell-surface receptor molecule that relays apoptotic (cell death) signals into cells. When Fas is activated by binding of its ligand, the proteolytic protein caspase-8 is recruited to a signalling complex known as DISC by binding to a Fas-associated adapter protein. A large new protein, FLASH, has now been identified by cloning of its complementary DNA. This protein contains a motif with oligomerizing activity whose sequence is similar to that of the Caenorhabditis elegans protein CED-4, and another domain (DRD domain) that interacts with a death-effector domain in caspase-8 or in the adapter protein. Stimulated Fas binds FLASH, so FLASH is probably a component of the DISC signalling complex. Transient expression of FLASH activates caspase-8, whereas overexpression of a truncated form of FLASH containing only one of its DRD or CED-4-like domains does not allow activation of caspase-8 and Fas-mediated apoptosis to occur. Overexpression of full-length FLASH blocks the anti-apoptotic effect of the adenovirus protein E1B19K. FLASH is therefore necessary for the activation of caspase-8 in Fas-mediated apoptosis.

Suggested Citation

  • Yuzuru Imai & Takaharu Kimura & Akira Murakami & Nobuyuki Yajima & Kazuhiro Sakamaki & Shin Yonehara, 1999. "The CED-4-homologous protein FLASH is involved in Fas-mediated activation of caspase-8 during apoptosis," Nature, Nature, vol. 398(6730), pages 777-785, April.
    • Handle: RePEc:nat:nature:v:398:y:1999:i:6730:d:10.1038_19709
    DOI: 10.1038/19709
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