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A downstream kinase of the mammalian target of rapamycin, p70S6K1, regulates human double minute 2 protein phosphorylation and stability
Author(s) -
Fang Jing,
Meng Qiao,
Vogt Peter K.,
Zhang Ruiwen,
Jiang BingHua
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20749
Subject(s) - phosphorylation , pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , ly294002 , kinase , biology , gene knockdown , autophagy related protein 13 , protein phosphorylation , protein kinase a , signal transduction , biochemistry , gene
Human double minute 2 (HDM2) is an oncoprotein overexpressed in many human cancers. HDM2 expression is regulated at multiple levels in cells. Phosphorylation of HDM2 plays an important role in its post‐translational regulation. In this study, we have shown that the phosphatidylinositol 3‐kinase (PI3K) inhibitor, LY294002, and the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, have similar effects on the inhibition of HDM2 phosphorylation and protein turnover. Rapamycin inhibited p70S6K1, but not AKT activation, indicating that rapamycin affects HDM2 phosphorylation via an AKT‐independent mechanism. Rapamycin also decreased HDM2 protein stability. Knockdown of p70S6K1 by a p70S6K1 siRNA resulted in the inhibition of HDM2 phosphorylation and a decrease in HDM2 protein turnover. Overexpression of p70S6K1 enhanced HDM2 phosphorylation and led to an increase in HDM2 protein turnover. Our results suggest that p70S6K1 regulates turnover of HDM2 protein for cancer development. J. Cell. Physiol. 209: 261–265, 2006. © 2006 Wiley‐Liss, Inc.