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Published on: May 14, 2016
Cell cycle-dependent regulation of TIAP/m-survivin expression
M Otaki1, M Hatano, K Kobayashi
1Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Abstract:
TIAP, a murine homologue of human survivin, is a member of the inhibitor of apoptosis (IAP) family and is specifically expressed at G2/M phase of the cell cycle. To elucidate regulatory mechanisms of the cycle-dependent expression, we have analyzed the promoter region of TIAP/mouse survivin (m-survivin). The 5'-flanking region of the TIAP/m-survivin gene contained a TATA-less promoter, two AP2 sites, three NF-kB sites, one Sp1 site, many cell cycle-dependent elements (CDEs) and one cell cycle gene homology region (CHR). Primer extension and 5'-rapid amplification of cDNA ends identified one transcription start site at position -100 upstream of the ATG start site (+1). TIAP/m-survivin promoter-luciferase analysis identified a minimal promoter region within the most proximal -271 bp upstream of the ATG start site, and the region between -410 and -272 was critical for the enhancer activity. The combination between the CHR at -51 and the CDE at -57 is also essential for the cell cycle-dependent expression. Mutation of the CDE/CHR element and the enhancer elements may cause disordered expression of TIAP/m-survivin to affect cell survival and oncogenesis.
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