Cell cycle-dependent regulation of TIAP/m-survivin expression.
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.
Otaki
M
M
Department of Developmental Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Hatano
M
M
Kobayashi
K
K
Ogasawara
T
T
Kuriyama
T
T
Tokuhisa
T
T
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002453:Cell Cycle; D005786:Gene Expression Regulation; D015723:Gene Library; D017930:Genes, Reporter; D051034:Inhibitor of Apoptosis Proteins; D051379:Mice; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D012689:Sequence Homology, Nucleic Acid; D000077022:Survivin
C107489:BIRC5 protein, human; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011506:Proteins; D012097:Repressor Proteins; D000077022:Survivin