Siah-1, SIP, and Ebi collaborate in a novel pathway for β-catenin degradation linked to p53 responses
Siah-1, SIP, and Ebi collaborate in a novel pathway for β-catenin degradation linked to p53 responses
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DOI：
10.1016/s1097-2765(01)00242-8
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发表时间：
2001-05-01
期刊：
影响因子：
16
通讯作者：
Reed, JC
中科院分区：
文献类型：
--
作者：
Matsuzawa, S;Reed, JC
β -catenin的破坏是通过与F box蛋白β -TrCP磷酸化依赖的相互作用来调节的。研究人员发现了一种新的β -catenin降解途径，涉及到与泛素偶联酶结合的果蝇Sina （Siah）和与β -TrCP识别的磷酸化位点无关的F box蛋白Ebi的哺乳动物同源物。在一系列蛋白质相互作用中，Siah通过与Sgt1同源物SIP结合而与Ebi物理连接，SIP结合Skp1 （Skp1 -Cullin-F盒复合物的中心成分）。Siah的表达是由p53诱导的，揭示了一种将基因毒性损伤与β -catenin破坏联系起来的方式，从而降低Tcf/LEF转录因子的活性，并有助于细胞周期阻滞。
Destruction of beta -catenin is regulated through phosphorylation-dependent interactions with the F box protein beta -TrCP. A novel pathway for beta -catenin degradation was discovered involving mammalian homologs of Drosophila Sina (Siah), which bind ubiquitin-conjugating enzymes, and Ebi, an F box protein that binds beta -catenin independent of the phosphorylation sites recognized by beta -TrCP. A series of protein interactions were identified in which Siah is physically linked to Ebi by association with a novel Sgt1 homolog SIP that binds Skp1, a central component of Skp1 -Cullin-F box complexes. Expression of Siah is induced by p53, revealing a way of linking genotoxic injury to destruction of beta -catenin, thus reducing activity of Tcf/LEF transcription factors and contributing to cell cycle arrest.