Cell cycle-dependent expression of cIAP2 at G2/M phase contributes to survival during mitotic cell cycle arrest.
cIAP2 (cellular inhibitor of apoptosis protein 2) is induced by NF-kappaB (nuclear factor kappaB) when cells need to respond quickly to different apoptotic stimuli. A recent study using cDNA microarray technology has suggested that cIAP2 transcription is regulated in a cell cycle-dependent manner, although the mechanism for such regulation is unknown. In this study, we confirmed the cell cycle-dependent regulation of cIAP2 expression at both the mRNA and protein levels. Additionally, we found that a bipartite CDE (cell cycle-dependent element)/CHR (cell cycle gene homology region) element in the cIAP2 promoter mediates cIAP2 gene activation in G2/M phase. Cell cycle-dependent G2/M-phase-specific cIAP2 expression is enhanced by NF-kappaB activation, and selective down-regulation of cIAP2 causes cells blocked in mitosis with nocodazole to become susceptible to apoptosis, indicating that the G2/M-phase-specific expression of cIAP2 contributes to the survival of mitotically arrested cells. Our studies describing the NF-kappaB-independent G2/M-phase-specific expression of cIAP2 will help in further understanding the molecular basis of cIAP2 over-expression in a variety of human cancers.
Jin
Hyung-Seung
HS
Department of Biology, Yonsei University, Seoul 120-749, Korea.
Lee
Tae H
TH
D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D001483:Base Sequence; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D016195:G2 Phase; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C494833:BIRC2 protein, human; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D015739:Nocodazole