Survivin-2B promotes autophagy by accumulating IKK alpha in the nucleus of selenite-treated NB4 cells.
Survivin-2B promotes autophagy by accumulating IKK alpha in the nucleus of selenite-treated NB4 cells.
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Survivin-2B 通过在亚硒酸盐处理的 NB4 细胞的细胞核中积累 IKK α 来促进自噬
DOI：
10.1038/cddis.2014.34
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发表时间：
2014-02-20
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
Survivin-2B是一种已知的Survivin剪接变异体，已被报道在一些癌细胞中促进细胞死亡，尽管它在另一些癌细胞中保持生存功能，但其机制尚不清楚。在这篇报道中，我们发现抗肿瘤药物亚硒酸盐在NB4细胞中将保护性自噬转换为凋亡。在这个过程中，Survivin-2B的表达水平降低，并减弱了IKKα与细胞核中Survivin-2B的相互作用，进而导致了核IKKα的减少。结果，已知的UVRAG转录因子p73表达下调。因此，自噬的起始者之一UVRAG的表达受到抑制。在NB4细胞和其他肿瘤细胞系(Jurkat、HCT116)中也证实了Survivin-2B的调节作用。体内实验证实，Survivin-2B、IKKα、p73和UVRAG的变化与体外相同。综上所述，Survivin-2B通过在细胞核中积聚和稳定IKKα促进自噬，并进一步调节细胞死亡。
Survivin-2B, a known splice variant of survivin, has been reported to promote cell death in some cancer cells, although it keeps prosurvival function in others, and the mechanisms are unclear. In this report, we discovered that selenite, an antitumor agent, switched protective autophagy to apoptosis in NB4 cells. In this process, the level of survivin-2B was decreased and the interaction between IKK alpha and survivin-2B in the nucleus was attenuated, which further led to the decrease of nuclear IKK alpha. As a result, P73, a known transcript factor of UVRAG, was downregulated. Therefore, the expression of UVRAG, one of the initiators of autophagy, was inhibited. The regulatory status of survivin-2B was also proved in NB4 cells after different chemicals’ exposure and in other tumor cell lines (Jurkat, HCT116). Finally, experiments in vivo confirmed that the alterations of survivin-2B, IKK alpha, P73 and UVRAG were the same as that in vitro. Taken together, survivin-2B promoted autophagy and further regulated cell death by accumulating and stabilizing IKK alpha in the nucleus.
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影响因子：
8
作者：
Al-Bahlani, S.;Fraser, M.;Wong, A. Y. C.;Sayan, B. S.;Bergeron, R.;Melino, G.;Tsang, B. K.
通讯作者：
Tsang, B. K.
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