Regulation of ribosomal protein S6 kinases by ubiquitination

被引：33

作者：

Wang, Mong-Lien ^{[1
]}

Panasyuk, Ganna ^{[1
,2
]}

Gwalter, Jodie ^{[1
]}

Nemazanyy, Ivan ^{[2
]}

Fenton, Tim ^{[1
,3
]}

Filonenko, Valeriy ^{[2
]}

Gout, Ivan ^{[1
,2
]}

机构：

[1] UCL, Dept Struct & Mol Biol, London WC1E 6BT, England

[2] Natl Acad Sci Ukraine, Inst Mol Biol & Genet, Kiev, Ukraine

[3] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2008年 / 369卷 / 02期

基金：

英国生物技术与生命科学研究理事会;

关键词：

signal transduction; ribosomal S6 kinases; polyubiquitination; regulation; stability;

D O I：

10.1016/j.bbrc.2008.02.032

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ribosomal protein S6 kinase (S6K) is a key player in the regulation of cell growth and energy metabolism via the mTOR and PI3K signalling pathways. The activity and subcellular localization of S6K are regulated by multiple S/T phosphorylations in response to diverse extracellular stimuli. Downregulation of S6K signalling occurs through the action of S/T phosphatases (PP2A and PP1) and tumor suppressors (TSC1/2 and PTEN). We report here that, in addition to phosphorylation, S6Ks are ubiquitinated in cells. The pattern of ubiquitination and the effect of proteasomal inhibitors on the steady-state level of transiently overexpressed and endogenous S6Ks point to proteasome-mediated degradation of ubiquitinated S6Ks. Furthermore, we found that the site(s) of ubiquitination are located in the kinase domain and that the N- and C-terminal regulatory regions modulate the efficiency of S6K ubiquitination. This study suggests that S6K signalling also could be regulated through the proteasome-mediated turnover of S6Ks. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：382 / 387

页数：6

共 17 条

[1] A novel N-terminal hydrophobic motif mediates constitutive degradation of serum- and glucocorticoid-induced kinase-1 by the ubiquitin-proteasome pathway [J].

Bogusz, Agata M. ;

Brickley, Deanna R. ;

Pew, Travis ;

Conzen, Suzanne D. .

FEBS JOURNAL, 2006, 273 (13) :2913-2928

[2] Phosphorylation of mammalian target of rapamycin (mTOR) at ser-2448 is mediated by p70S6 kinase [J].

Chiang, GG ;

Abraham, RT .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (27) :25485-25490

[3]

COFFER P, 1994, BIOCHEM BIOPH RES CO, P780

[4] The ubiquitin-proteasome system and cancer [J].

Devoy, A ;

Soane, T ;

Welchman, R ;

Mayer, RJ .

ESSAYS IN BIOCHEMISTRY, VOL 41: THE UBIQUITIN-PROTEASOME SYSTEM, 2005, 41 :187-203

[5] Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6 kinase β containing a proline-rich region [J].

Gout, I ;

Minami, T ;

Hara, K ;

Tsujishita, Y ;

Filonenko, V ;

Waterfield, MD ;

Yonezawa, K .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (46) :30061-30064

[6] The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins [J].

Harrington, LS ;

Findlay, GM ;

Gray, A ;

Tolkacheva, T ;

Wigfield, S ;

Rebholz, H ;

Barnett, J ;

Leslie, NR ;

Cheng, S ;

Shepherd, PR ;

Gout, I ;

Downes, CP ;

Lamb, RE .

JOURNAL OF CELL BIOLOGY, 2004, 166 (02) :213-223

[7] Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase [J].

Holz, MK ;

Blenis, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (28) :26089-26093

[8] Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function [J].

Jastrzebski, Katarzyna ;

Hannan, Katherine M. ;

Tchoubrieva, Elissaveta B. ;

Hannan, Ross D. ;

Pearson, Richard B. .

GROWTH FACTORS, 2007, 25 (04) :209-226

[9] Characterization of S6K2, a novel kinase homologous to S6K1 [J].

Lee-Fruman, KK ;

Kuo, CJ ;

Lippincott, J ;

Terada, N ;

Blenis, J .

ONCOGENE, 1999, 18 (36) :5108-5114

[10] Activation of protein kinase C triggers its ubiquitination and degradation [J].

Lu, ZM ;

Liu, D ;

Hornia, A ;

Devonish, W ;

Pagano, M ;

Foster, DA .

MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (02) :839-845

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