Phosphorylation of ARD1 by IKKbeta contributes to its destabilization and degradation.
Phosphorylation of ARD1 by IKKbeta contributes to its destabilization and degradation.
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DOI：
10.1016/j.bbrc.2009.08.127
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发表时间：
2009-11-06
影响因子：
3.1
通讯作者：
Hung, Mien-Chie
中科院分区：
文献类型：
--
作者：
Kuo, Hsu-Ping;Lee, Dung-Fang;Xia, Weiya;Lai, Chien-Chen;Li, Long-Yuan;Hung, Mien-Chie
IκB激酶β（IKKβ）是多种促炎信号下游的主要激酶，通过磷酸化和调节其底物介导多种细胞功能。在蛋白质序列分析的基础上，我们鉴定了抑制缺陷蛋白1（ARD1）作为一种新的IKKβ底物，ARD1是一种参与许多人类癌细胞凋亡和细胞增殖过程的蛋白质。我们提供的证据表明，ARD1确实是IKKβ的真正底物。IKKβ与ARD1物理结合并在Ser209磷酸化。IKKβ的磷酸化使ARD1不稳定，并诱导其蛋白酶体介导的降解。与ARD1非磷酸化突变体（S209A）转染细胞相比，在ARD1磷酸化模拟突变体（S209E）转染细胞中观察到生长抑制受损。我们对ARD1和IKKβ之间分子相互作用的研究结果可能有助于进一步了解ARD1的上游调控机制和IKKβ的多种功能。
IκB kinase β (IKKβ), a major kinase downstream of various proinflammatory signals, mediates multiple cellular functions through phosphorylation and regulation of its substrates. On the basis of protein sequence analysis, we identified arrest-defective protein 1 (ARD1), a protein involved in apoptosis and cell proliferation processes in many human cancer cells, as a new IKKβ substrate. We provided evidence showing that ARD1 is indeed a bona fide substrate of IKKβ. IKKβ physically associated with ARD1 and phosphorylated it at Ser209. Phosphorylation by IKKβ destabilized ARD1 and induced its proteasome-mediated degradation. Impaired growth suppression was observed in ARD1 phosphorylation-mimic mutant (S209E)-transfected cells as compared with ARD1 non-phosphorylatable mutant (S209A)-transfected cells. Our findings of molecular interactions between ARD1 and IKKβ may enable further understanding of the upstream regulation mechanisms of ARD1 and of the diverse functions of IKKβ.
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影响因子：
4.8
作者：
Fisher, TS;Des Etages, S;Li, BY
通讯作者：
Li, BY
影响因子：
4.8
作者：
Bilton, R;Mazure, N;Brahimi-Horn, MC
通讯作者：
Brahimi-Horn, MC
影响因子：
3.5
作者：
Murray-Rust, TA;Oldham, NJ;Schofield, CJ
通讯作者：
Schofield, CJ
影响因子：
5.3
作者：
WHITEWAY, M;FREEDMAN, R;THORNER, J
通讯作者：
THORNER, J
DOI：
10.1083/jcb.200708090
发表时间：
2007-11-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Yi CH;Sogah DK;Boyce M;Degterev A;Christofferson DE;Yuan J
通讯作者：
Yuan J