Interaction between survivin and aurora-B kinase plays an important role in survivin-mediated up-regulation of human telomerase reverse transcriptase expression.
Survivin, a member of the apoptosis inhibitor family, shows increased expression in human cancers of various origins. It has been demonstrated that survivin inhibits apoptosis via caspase inhibition and promotes mitosis via aurora-B kinase activation. We recently reported that survivin enhances the expression of human telomerase reverse transcriptase (hTERT), a major determinant of telomerase activity in colon cancer cells. Survivin up-regulates hTERT expression by promoting the expression of specificity protein-1 (Sp1)- and c-Myc-mediated gene transcription via enhancing the phosphorylation of these transcriptional factors. However, the mechanism by which survivin regulates the phosphorylation of Sp1 and c-Myc is not well defined. In the present study, we hypothesized that survivin promotes the phosphorylation of Sp1 and c-Myc by activating aurora-B kinase. Inhibition of this enzyme by introducing small inhibitory RNA attenuated the phosphorylation of Sp1 and c-Myc and resulted in the abolition of the survivin effect on hTERT expression. In addition, blocking survivin phosphorylation at a threonine residue by inhibiting cyclin-dependent kinase 1 caused the dissociation of aurora-B kinase from survivin and attenuated the up-regulation of hTERT expression by survivin. Taken together, these results suggest that the interaction between survivin and aurora-B kinase may be essential for survivin to increase hTERT expression.
Furuya
Momoko
M
Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8543, Japan.
Tsuji
Naoki
N
Kobayashi
Daisuke
D
Watanabe
Naoki
N
D064107:Aurora Kinase B; D064127:Aurora Kinases; D016203:CDC2 Protein Kinase / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008954:Models, Biological; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D000077022:Survivin; D019098:Telomerase / Q000096:biosynthesis* / Q000378:metabolism
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D016329:Sp1 Transcription Factor; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D019098:Telomerase