Elsevier

Genomics

Volume 84, Issue 3, September 2004, Pages 587-591
Genomics

Short Communication
Caspase-1ζ, a new splice variant of the caspase-1 gene

https://doi.org/10.1016/j.ygeno.2004.06.005Get rights and content

Abstract

Five alternatively spliced mRNA isoforms of human caspase-1 have been identified previously and we report here the cloning of a new isoform, named CASP1 zeta (ζ), from human ovarian surface epithelial cell cDNA. The new isoform ζ is identical to the α isoform but missing 79 nucleotides in the coding region of the prodomain of procaspase-1. Analysis of the cDNA sequence of the ζ isoform revealed an ORF of a shorter protein missing the 39 amino acids at the amino terminal of procaspase-1α, which comprises the important caspase activating recruitment domain (CARD), which is required for interactions between caspases and other proteins. Secondary structure analysis of procaspase-1 CARD predicted the truncation of the α1, the α2, and part of the α3 helix in the ζ isoform in comparison to the full-length α isoform. The new ζ isoform was expressed in many, but not all, adult human tissues by RT-PCR. In HEK293 cells, transient overexpression of wild-type caspase-1ζ induced apoptosis to levels similar to those of caspase-1α. However, mutational change at the caspase-1 active center of the Cys 246 of caspase-1ζ, as well as Cys 285 of caspase-1α, completely abolished their apoptotic activity. Our findings suggest that caspase-1ζ is a widespread, new proapoptotic isoform of caspase-1. They also demonstrate that the first 39 amino acids of the N-terminal of the CARD in procaspase-1 are not required for its apoptotic activity.

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Acknowledgment

The project was supported by a grant to N.A. from the National Cancer Institute of Canada, with funds from the Canadian Cancer Society.

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    Sequence data from this article have been deposited with the GenBank Data Library under Accession No. AY660536.

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