| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 92 === Apoptosis, or programmed cell death, is a cellular suicide induced by environmental stresses or stimulation of the cytokines. Mitochondria apoptotic pathway is a main pathway in response to intrinsic cellular damages. Caspase-9, which transmits death signals by activating itself is an important initiator in the mitochondria pathway. There are two caspase-9 isoforms, caspase-9 and caspase-9b (also called caspase-9s). In the present study, we identify the third isoform of caspase-9, named caspase-9c, from the human fetal liver cDNA library. The nucleotide sequence of caspase-9c is highly identical to the sequence of caspase-9, except a deletion of 140 bp, probably due to a non-canonical splice mechanism. Caspase-9c encodes a ninety-five amino acid protein, with ninety-three amino acids identical to caspas-9 CARD (caspase recruitment domain). Caspase-9c expresses ubiquitously in a variety of cell lines and tissues, represented by RT-PCR and confirmed with DNA sequencing. Unlike CARD, overexpression of caspase-9c fails to increase the activity of NF-B, to attenuate apoptosome-dependent activation of caspase-9 and to prevent cytochrome c/ Apaf-1 dependent cell death, induced by UV and cisplatin (CDDP). Surprisingly, however, caspase-9c protects SH-SY5Y cells from serum depletion-induced apoptosis. These results suggest that caspase-9c plays a crucial role in regulating serum depletion-induced apoptosis, independent of apoptosome and NF-B signaling.
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