Interaction between survivin and aurora-B kinase plays an important role in survivin-mediated up-regulation of human telomerase reverse transcriptase expression
Interaction between survivin and aurora-B kinase plays an important role in survivin-mediated up-regulation of human telomerase reverse transcriptase expression
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DOI：
10.3892/ijo_00000232
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发表时间：
2009-04-01
影响因子：
5.2
通讯作者：
Watanabe, Naoki
中科院分区：
文献类型：
--
作者：
Furuya, Momoko;Tsuji, Naoki;Watanabe, Naoki
Survivin是凋亡抑制因子家族的一员，在各种来源的人类癌症中表达增加。已经证明，生存素通过抑制半胱天冬酶抑制凋亡，并通过激活极光-B激酶促进有丝分裂。我们最近报道，生存素增强人端粒酶逆转录酶（hTERT）的表达，端粒酶活性的主要决定因素在结肠癌细胞。Survivin通过增强特异性蛋白1（Sp1）和c-Myc介导的基因转录因子的磷酸化，促进这些转录因子的表达，从而上调hTERT的表达。然而，生存素调节Sp1和c-Myc磷酸化的机制还不清楚。在本研究中，我们假设生存素通过激活Aurora-B激酶促进Sp1和c-Myc的磷酸化。通过引入小的抑制性RNA来抑制这种酶，减弱了Sp1和c-Myc的磷酸化，并导致生存素对hTERT表达的影响被取消。此外，通过抑制细胞周期蛋白依赖性激酶I来阻断存活素在苏氨酸残基处的磷酸化，导致极光-B激酶从存活素解离，并减弱存活素对hTERT表达的上调。总之，这些结果表明，生存素和极光-B激酶之间的相互作用可能是生存素增加hTERT表达所必需的。
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 I 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.