Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis

Srinivasula, S. M., Ahmad, M., Guo, Y., Zhan, Y., Lazebnik, Y., Fernandes-Alnemri, T., Alnemri, E. S. (1999) Identification of an endogenous dominant-negative short isoform of caspase-9 that can regulate apoptosis. Cancer Research, 59 (5). pp. 999-1002. ISSN 0008-5472

URL: http://www.ncbi.nlm.nih.gov/pubmed/10070954

Abstract

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.

Item Type: Paper
Uncontrolled Keywords: Alternative Splicing Amino Acid Sequence Apoptosis Base Sequence Binding Sites Caspase 9 Caspases Cell Line Cloning, Molecular HeLa Cells Humans Isoenzymes Jurkat Cells Molecular Sequence Data Polymerase Chain Reaction Protein Biosynthesis RNA, Messenger Recombinant Proteins Reverse Transcriptase Polymerase Chain Reaction Sequence Alignment Sequence Homology, Amino Acid Transcription, Genetic Tumor Cells, Cultured
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions
CSHL Authors:
Communities: CSHL labs > Labeznik lab
Depositing User: Matt Covey
Date: 1999
Date Deposited: 12 Dec 2012 17:30
Last Modified: 12 Dec 2012 17:30
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26394

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