Threonine 22 Phosphorylation Attenuates Hsp90 Interaction with Cochaperones and Affects Its Chaperone Activity

被引：133

作者：

Mollapour, Mehdi ^{[1
]}

Tsutsumi, Shinji ^{[1
]}

Truman, Andrew W. ^{[3
]}

Xu, Wanping ^{[1
]}

Vaughan, Cara K. ^{[4
]}

Beebe, Kristin ^{[1
]}

Konstantinova, Anna ^{[1
]}

Vourganti, Srinivas ^{[1
]}

Panaretou, Barry ^{[5
]}

Piper, Peter W. ^{[3
]}

Trepel, Jane B. ^{[2
]}

Prodromou, Chrisostomos ^{[6
]}

Pearl, Laurence H. ^{[6
]}

Neckers, Len ^{[1
]}

机构：

[1] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA

[2] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA

[3] Univ Sheffield, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England

[4] Birkbeck Coll, Sch Crystallog, Inst Struct & Mol Biol, London WC1E 7HZ, England

[5] Kings Coll London, Div Pharmaceut Sci, London SE1 9NH, England

[6] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9QR, E Sussex, England

来源：

MOLECULAR CELL | 2011年 / 41卷 / 06期

关键词：

HEAT-SHOCK-PROTEIN; CASEIN KINASE-II; STEROID-RECEPTOR; CONFORMATIONAL STATES; MOLECULAR CHAPERONES; CLIENT PROTEINS; ATP HYDROLYSIS; IN-VIVO; YEAST; CYCLE;

D O I：

10.1016/j.molcel.2011.02.011

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：

Heat shock protein 90 (Hsp90) is an essential molecular chaperone whose activity is regulated not only by cochaperones but also by distinct posttranslational modifications. We report here that casein kinase 2 phosphorylates a conserved threonine residue (T22) in alpha helix-1 of the yeast Hsp90 N-domain both in vitro and in vivo. This a helix participates in a hydrophobic interaction with the catalytic loop in Hsp90's middle domain, helping to stabilize the chaperone's ATPase-competent state. Phosphomimetic mutation of this residue alters Hsp90 ATPase activity and chaperone function and impacts interaction with the cochaperones Aha1 and Cdc37. Overexpression of Aha1 stimulates the ATPase activity, restores cochaperone interactions, and compensates for the functional defects of these Hsp90 mutants.

引用

页码：672 / 681

页数：10

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