Characterization of a Novel Isoform of Caspase-9 That Inhibits Apoptosis

James M Angelastro, Nah Yong Moon, David X. Liu, An Suei Yang, Lloyd A. Greene, Thomas F. Franke

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

We have identified a novel isoform of rat caspase-9 in which the C terminus of full-length caspase-9 is replaced with an alternative peptide sequence. Casp-9-CTD (where CTD is carboxyl-terminal divergent) is expressed in multiple tissues, with the relative highest expression observed in ovary and heart. Casp-9-CTD was found primarily in the cytoplasm and was not detected in the nucleus. Structural predictions suggest that in contrast to full-length caspase-9, casp-9-CTD will not be processed. Our model is supported by reduced protease activity of casp-9-CTD preparations in vitro and by the lack of detectable processing of casp-9-CTD proenzyme or the induction of cell death following transfection into cells. Both neuronal and non-neuronal cell types transfected with casp-9-CTD were resistant to death evoked by trophic factor deprivation or DNA damage. In addition, cytosolic lysates prepared from cells permanently expressing exogenous casp-9-CTD were resistant to caspase induction by cytochrome c in reconstitution assays. Taken together, our observations indicate that casp-9-CTD acts as a dominant-negative variant. Its expression in various tissues indicates a physiological role in regulating cell death.

Original languageEnglish (US)
Pages (from-to)12190-12200
Number of pages11
JournalJournal of Biological Chemistry
Volume276
Issue number15
DOIs
StatePublished - Apr 13 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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