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

TIAP, a murine homologue of human surviving 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 expre ssion, we have analyzed the promoter region of TIAP/mouse survivin (m-survi vin). The 5'-flanking region of the TIAP/m-survivin gene contained a TATA-l ess promoter, two AP2 sites, three NF-kB sites, one Spl site, many cell cyc le-dependent elements (CDEs) and one cell cycle gene homology region (CHR). Primer extension and 5'-rapid amplification of cDNA ends identified one tr anscription start site at position -100 upstream of the ATG start site (+1) . TIAP/m-survivin promoter-luciferase analysis identified a minimal promote r region within the most proximal -271 bp upstream of the ATG start site, a nd 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 essentia l for the cell cycle-dependent expression. Mutation of the CDE/CHR element and the enhancer elements may cause disordered expression of TIAP/m-survivi n to affect cell survival and oncogenesis. (C) 2000 Elsevier Science B.V. A ll rights reserved.