Casein kinase-2 mediates cell survival through phosphorylation and degradation of inositol hexakisphosphate kinase-2

被引：40

作者：

Chakraborty, Anutosh ^{[1
]}

Werner, J. Kent, Jr. ^{[1
]}

Koldobskiy, Michael A. ^{[1
]}

Mustafa, Asif K. ^{[1
]}

Juluri, Krishna R. ^{[1
]}

Pietropaoli, Joseph ^{[1
]}

Snowman, Adele M. ^{[1
]}

Snyder, Solomon H. ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 06期

关键词：

KAPPA-B ACTIVATION; CK2; INHIBITORS; PYROPHOSPHATES; FAMILY; CARCINOMA; BETA;

D O I：

10.1073/pnas.1019381108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The inositol pyrophosphate, diphosphoinositol pentakisphosphate, regulates p53 and protein kinase Akt signaling, and its aberrant increase in cells has been implicated in apoptosis and insulin resistance. Inositol hexakisphosphate kinase-2 (IP6K2), one of the major inositol pyrophosphate synthesizing enzymes, mediates p53-linked apoptotic cell death. Casein kinase-2 (CK2) promotes cell survival and is upregulated in tumors. We show that CK2 mediated cell survival involves IP6K2 destabilization. CK2 physiologically phosphorylates IP6K2 at amino acid residues S347 and S356 contained within a PEST sequence, a consensus site for ubiquitination. HCT116 cells depleted of IP6K2 are resistant to cell death elicited by CK2 inhibitors. CK2 phosphorylation at the degradation motif of IP6K2 enhances its ubiquitination and subsequent degradation. IP6K2 mutants at the CK2 sites that are resistant to CK2 phosphorylation are metabolically stable.

引用

页码：2205 / 2209

页数：5

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