Molecular ordering of the cell death pathway: Bcl-2 and Bcl-xL function upstream of the ced-3-like apoptotic proteases

Arul M. Chinnaiyan, Kim Orth, Karen O'Rourke, Hangjun Duan, Guy G. Poirier, Vishva M. Dixit

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592 Scopus citations

Abstract

Genetic analyses of Caenorhabditis elegans has identified three genes that function in the regulation of nematode cell death. Mammalian homologs of two of these genes, ced-9 and ced-3, have been identified and comprise proteins belonging to the Bcl-2 and ICE families, respectively. To date, it is unclear where the negative regulators, ced-9 and bcl-2, function relative to the death effectors, ced-3 and the mammalian ced-3 homologs, respectively. Here, the molecular order of the cell death pathway is defined. Our results establish that Bcl-2 and Bcl-xL function upstream of two members of the ICE/ CED-3 family of cysteine proteases, Yama (CPP32/apopain) and ICE-LAPS (Mch3).

Original languageEnglish (US)
Pages (from-to)4573-4576
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number9
StatePublished - Mar 1 1996

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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