CK2 functionally interacts with AKT/PKB to promote the β-catenin-dependent expression of survivin and enhance cell survival
CK2 functionally interacts with AKT/PKB to promote the β-catenin-dependent expression of survivin and enhance cell survival
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DOI：
10.1007/s11010-011-0965-4
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发表时间：
2011-10-01
影响因子：
4.3
通讯作者：
Tapia, Julio C.
中科院分区：
文献类型：
--
作者：
Ponce, Daniela P.;Yefi, Roger;Tapia, Julio C.
β-连环蛋白在经典Wnt信号通路中至关重要。这一途径被CK 2上调，CK 2与抗凋亡蛋白生存素的表达增强有关，但其潜在的分子机制尚不清楚。AKT/PKB激酶磷酸化并促进β-连环蛋白转录活性，而CK 2通过Ser 129磷酸化过度激活AKT;然而，这种磷酸化对β-连环蛋白转录活性和细胞存活的作用尚不清楚。我们在HEK-293 T细胞中研究了CK 2依赖的AKT过度激活对细胞活力的影响，以及分析了β-连环蛋白亚细胞定位和转录活性以及生存素表达。CK 2 α过表达导致生存素的β-连环蛋白依赖性转录和蛋白水平增加，从而增强对凋亡的抵抗。然而，CK 2 α增强效应逆转时，一个AKT突变体的Ser 129磷酸化缺陷CK 2共表达。因此，我们的研究结果强烈表明，CK 2 α特异性增强β-连环蛋白转录活性以及细胞存活可能取决于CK 2的AKT超活化。
beta-Catenin is crucial in the canonical Wnt signaling pathway. This pathway is up-regulated by CK2 which is associated with an enhanced expression of the antiapoptotic protein survivin, although the underlying molecular mechanism is unknown. AKT/PKB kinase phosphorylates and promotes beta-catenin transcriptional activity, whereas CK2 hyperactivates AKT by phosphorylation at Ser129; however, the role of this phosphorylation on beta-catenin transcriptional activity and cell survival is unclear. We studied in HEK-293T cells, the effect of CK2-dependent hyperactivation of AKT on cell viability, as well as analyzed beta-catenin subcellular localization and transcriptional activity and survivin expression. CK2 alpha overexpression led to an augmented beta-catenin-dependent transcription and protein levels of survivin, and consequently an enhanced resistance to apoptosis. However, CK2 alpha-enhancing effects were reversed when an AKT mutant deficient in Ser129 phosphorylation by CK2 was co-expressed. Therefore, our results strongly suggest that CK2 alpha-specific enhancement of beta-catenin transcriptional activity as well as cell survival may depend on AKT hyperactivation by CK2.