Cell cycle-dependent regulation of TIAP/m-survivin expression

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.