The Skp2 Promoter Integrates Signaling through the NF-κB, p53, and Akt/GSK3β Pathways to Regulate Autophagy and Apoptosis (Retracted article. See vol. 55, pg. 342, 2014)
The Skp2 Promoter Integrates Signaling through the NF-κB, p53, and Akt/GSK3β Pathways to Regulate Autophagy and Apoptosis (Retracted article. See vol. 55, pg. 342, 2014)
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DOI：
10.1016/j.molcel.2010.03.018
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发表时间：
2010-05-28
期刊：
影响因子：
16
通讯作者：
Perkins, Neil D.
中科院分区：
文献类型：
--
作者：
Barre, Benjamin;Perkins, Neil D.
NF-κ B和p53是细胞应激反应的重要调节因子。在这里，我们确定Skp 2基因作为DNA损伤后的NF-κ B和p53靶点。然而，Skp 2表达可以以需要p52 NF-κ B亚基和p53的方式被诱导或抑制，随后影响自噬、凋亡和p53功能。这一过程由Akt（PKB）/GSK 3 β途径调节。当Akt被激活时，GSK 3 β被抑制，允许p52和p53协同诱导Skp 2表达。然而，如果Akt失活，GSK 3 β磷酸化p52的Ser 222。这种修饰破坏了p52同源二聚体/Bcl-3复合物，并促进了p52/c-Rel的转录抑制。因此，Skp 2启动子通过NF-κ B、p53和Akt/GSK 3 β途径整合信号传导，以响应DNA损伤调节细胞命运。
NF-kappa B and p53 are important regulators of the cellular response to stress. Here, we identify the Skp2 gene as being both an NF-kappa B and p53 target after DNA damage. However, Skp2 expression can be either induced or repressed in a manner requiring both the p52 NF-kappa B subunit and p53, with subsequent effects on autophagy, apoptosis, and p53 function. This process is regulated by the Akt(PKB)/ GSK3 beta pathway. When Akt is active, GSK3 beta is repressed, allowing p52 and p53 to cooperatively induce Skp2 expression. However, if Akt is inactive, GSK3 beta phosphorylates p52 at Ser 222. This modification disrupts p52 homodimer/Bcl-3 complexes and facilitates transcriptional repression by p52/c-Rel. The Skp2 promoter therefore integrates signaling through the NF-kappa B, p53, and Akt/GSK3 beta pathways to regulate cell fate in response to DNA damage.