mTOR-raptor binds and activates SGK1 to regulate p27 phosphorylation (Mol Cell, 2008, 30:701-711)

報告日期: 2008/10/31
報告時間: 16:00/16:50
報告學生: 鄧喬方
講評老師: 徐麗君
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971031-2.pdf

mTOR-Raptor Binds and Activates SGK1 to Regulate p27 Phosphorylation

 

Molecular Cell 30, 701-711 (2008)

 

Speaker: 鄧喬方

Commentator: 徐麗君 老師

Date: 2008.10.31, pm 4:00-4:50

Place: room 602

 

Abstract:

    The mammalian target of rapamycin (mTOR) is a central regulator of cell growth. The mTORC1 complex, comprising mTOR, raptor, and mLST8, regulates protein synthesis through phosphorylation of p70S6K1 and 4EBP1. The cell-cycle effects of mTORC1 (mTOR-raptor) are not fully understood. p27 is a cyclin-dependent kinase (Cdk) inhibitor that regulates G0 to S phase transitions of cell cycle by inhibiting cyclin E-Cdk2 complexes. In this study, the authors found that cellular mTOR activation, by mTOR overexpression or by refeeding of amino acid-deprived cells or by TSC2 shRNA, activated SGK1 and caused p27 phosphorylation and cytoplasmic mislocalization, and both were inhibited by rapamycin or raptor shRNA. Knockdown of SGK1 impaired p27 phosphorylation at T157 following activation of cellular mTOR. The result from immunoprecipitation, GST pull-down assay, and kinase assay showed that mTORC1 bound and phosphorylated SGK1 and that SGK1 phosphorylated p27. These data provide evidence that mTORC1 may promote G1 progression and

deregulate the cell cycle through SGK1-mediated p27 dysfunction.

 

References:

1. Jiang BH and Liu LZ (2008). Role of mTOR in anticancer drug resistance:

perspectives for improved drug treatment. Drug Resist Updat 11, 63-76.

2. Chu IM, Hengst L and Slingerland JH (2008). The Cdk inhibitor p27 in

   human cancer: prognostic potential and relevance to anticancer therapy.

Nat Rev Cancer 8, 253-267.