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Biochem Biophys Res Commun 2010 Apr 16;3944:966-71. doi: 10.1016/j.bbrc.2010.03.099.
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Homeodomain-interacting protein kinase 2 (HIPK2) targets beta-catenin for phosphorylation and proteasomal degradation.

Kim EA , Kim JE , Sung KS , Choi DW , Lee BJ , Choi CY .

The regulation of intracellular beta-catenin levels is central in the Wnt/beta-catenin signaling cascade and the activation of the Wnt target genes. Here, we show that homeodomain-interacting protein kinase 2 (HIPK2) acts as a negative regulator of the Wnt/beta-catenin pathway. Knock-down of endogenous HIPK2 increases the stability of beta-catenin and results in the accumulation of beta-catenin in the nucleus, consequently enhancing the expression of Wnt target genes and cell proliferation both in vivo and in cultured cells. HIPK2 inhibits TCF/LEF-mediated target gene activation via degradation of beta-catenin. HIPK2 phosphorylates beta-catenin at its Ser33 and Ser37 residues without the aid of a priming kinase. Substitutions of Ser33 and Ser37 for alanines abolished the degradation of beta-catenin associated with HIPK2. In ex vivo mouse model, HIPK2 knock-down resulted in accumulation of beta-catenin, thereby potentiated beta-catenin-mediated cell proliferation and tumor formation. Furthermore, the axis duplication induced by the ectopic expression of beta-catenin was blocked by co-injection of HIPK2 mRNAs into Xenopus embryos. Taken together, HIPK2 appears to function as a novel negative regulator of beta-catenin through its phosphorylation and proteasomal degradation.

PubMed ID: 20307497
Article link: Biochem Biophys Res Commun

Species referenced: Xenopus
Genes referenced: ccnd1 ctnnb1 gsc hipk2 nodal3.1 nodal3.2 sia1

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