Phosphorylation of ARD1 by IKKbeta contributes to its destabilization and degradation.
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Kuo HP, Lee DF, Xia W, Lai CC, Li LY, Hung MC
Phosphorylation of ARD1 by IKKbeta contributes to its destabilization and degradation.
Biochem Biophys Res Commun. 2009 Nov 6;389(1):156-61. doi: 10.1016/j.bbrc.2009.08.127. Epub 2009 Aug 28.
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- 19716809 [ View in PubMed]
- Abstract
IkappaB kinase beta (IKKbeta), 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 IKKbeta substrate. We provided evidence showing that ARD1 is indeed a bona fide substrate of IKKbeta. IKKbeta physically associated with ARD1 and phosphorylated it at Ser209. Phosphorylation by IKKbeta 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 IKKbeta may enable further understanding of the upstream regulation mechanisms of ARD1 and of the diverse functions of IKKbeta.