Cloning of a novel human caspase-9 splice variant containing only the CARD domain.
Caspase-9 plays a key role in the intrinsic apoptotic pathway and currently two splice variants (caspase-9-alpha and -beta) have been identified. The present study cloned and characterized a novel caspase-9 splice variant, hereby designated Casp9-gamma. Casp9-gamma is generated from an additional alternative 3' splice site in the fourth exon of caspase-9, resulting in a 58-nucleotide fragment insertion compared with the full-length caspase-9-alpha. The fragment introduces an in-frame stop codon, and the resulting open reading frame (ORF) is preterminated. The Casp9-gamma comprises the deduced 154 amino acid residues containing only the caspase recruitment domain (CARD) and does not contain the large and small subunits. The Casp9-gamma does not promote apoptosis when overexpressed in mammalian cells. Moreover, it inhibits the cleavage of procaspase-3 mediated by proapoptotic member Bax or apoptosis inductor staurosporine. Therefore, Casp9-gamma may function as an endogenous apoptotic inhibitor by interfering with the CARD-CARD interaction between Apaf-1 (apoptotic protease activating factor-1) and procaspase-9. In addition, Casp9-gamma does not enhance NF-kappaB activation in transfected 293T cells, conflicting with previous evidence that the isolated CARD of caspase-9 activates NF-kappaB in ND7 cells. This suggests that the procaspase-9-mediated NF-kappaB activation in response to cellular stresses is cell type-specific through an unidentified mechanism.
Wang
Pingzhang
P
Chinese National Human Genome Center, Beijing. #3-707 North YongChang Road BDA, Beijing 100176, PR China. sicau2000@yahoo.com.cn
Shi
Taiping
T
Ma
Dalong
D
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D053453:Caspase 9; D020169:Caspases / Q000235:genetics* / Q000502:physiology; D020134:Catalytic Domain / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019295:Computational Biology; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D017434:Protein Structure, Tertiary
D016328:NF-kappa B; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases