Isoform of Caspase-9 That Can Regulate Apoptosis Identification of an Endogenous Dominant-Negative Short

نویسندگان

  • Srinivasa M. Srinivasula
  • Manzoor Ahmad
  • Yin Guo
  • Yi Zhan
  • Yuri Lazebnik
  • Teresa Fernandes-Alnemri
  • Emad S. Alnemri
چکیده

Alternatively spliced isoforms of certain apoptosis regulators, such as Bcl-x, Ced-4, and Ich-1, have been shown to play opposing roles in regulating apoptosis. Here, we describe the identification of an endogenous alternatively spliced isoform of caspase-9, named caspase-9b, which lacks the central large subunit caspase domain. Caspase-9b is detectable in many cell lines by PCR and at the mRNA and protein levels. Caspase-9b can interact with the caspase recruitment domain of Apaf-1, and like the active site mutant of caspase-9, it can inhibit multiple forms of apoptosis, including those triggered by oligomerization of death receptors. It can also block activation of caspase-9 and -3 by Apaf-1 in an in vitro cytochrome c-dependent caspase activation assay. These results suggest that caspase-9b functions as an endogenous apoptosis inhibitory molecule by interfering with the formation of a functional Apaf-1-caspase-9 complex.

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تاریخ انتشار 1999