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

Research output: Contribution to journalArticle

592 Scopus citations


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
Issue number9
StatePublished - Mar 1 1996


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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