The human caspase-2 gene: alternative promoters, pre-mRNA splicing and AUG usage direct isoform-specific expression.

摘要: Caspases have been shown to play important roles in apoptotic cell death, cytokine maturation and differentiation. However, the transcriptional regulation of corresponding CASP genes remains poorly known. We describe a 5.1 kb fragment located upstream first translated exon human CASP-2 gene, which is known encode caspase-2L -2S protein isoforms. Transient transfection experiments, together with transcription start site mapping transcript analysis, demonstrate that each caspase mRNA initiated from separate promoter regions, produced alternative splicing events these regions. The CASP-2L much stronger than CASP-2S promoter, good agreement respective levels two caspases. In addition, several in-frame translational sites can be identified for isoform, one common both, present second exon, used efficiently. Surprisingly, short isoform may also at downstream AUG codon within same exon. Thus, strength, initiation 5'-splicing regulate expression main caspase-2 isoforms translation codons.