Rictor Forms a Complex with Cullin-1 to Promote SGK1 Ubiquitination and Destruction

Daming Gao, Lixin Wan, Hiroyuki Inuzuka, Anders H. Berg, Alan Tseng, Bo Zhai, Shavali Shaik, Eric Bennett, Adriana E. Tron, Jessica A. Gasser, Alan Lau, Steven P. Gygi, J. Wade Harper, James A. DeCaprio, Alex Toker, Wenyi Wei

研究成果: Article査読

75 被引用数 (Scopus)

抄録

The Rictor/mTOR complex (also known as mTORC2) plays a critical role in cellular homeostasis by phosphorylating AGC kinases such as Akt and SGK at their hydrophobic motifs to activate downstream signaling. However, the regulation of mTORC2 and whether it has additional function(s) remain largely unknown. Here, we report that Rictor associates with Cullin-1 to form a functional E3 ubiquitin ligase. Rictor, but not Raptor or mTOR alone, promotes SGK1 ubiquitination. Loss of Rictor/Cullin-1-mediated ubiquitination leads to increased SGK1 protein levels as detected in Rictor null cells. Moreover, as part of a feedback mechanism, phosphorylation of Rictor at T1135 by multiple AGC kinases disrupts the interaction between Rictor and Cullin-1 to impair SGK1 ubiquitination. These findings indicate that the Rictor/Cullin-1 E3 ligase activity is regulated by a specific signal relay cascade and that misregulation of this mechanism may contribute to the frequent overexpression of SGK1 in various human cancers.

本文言語English
ページ(範囲)797-808
ページ数12
ジャーナルMolecular Cell
39
5
DOI
出版ステータスPublished - 2010 9月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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