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Publication : Conductin/axin2 and Wnt signalling regulates centrosome cohesion.

First Author  Hadjihannas MV Year  2010
Journal  EMBO Rep Volume  11
Issue  4 Pages  317-24
PubMed ID  20300119 Mgi Jnum  J:164744
Mgi Id  MGI:4835108 Doi  10.1038/embor.2010.23
Citation  Hadjihannas MV, et al. (2010) Conductin/axin2 and Wnt signalling regulates centrosome cohesion. EMBO Rep 11(4):317-24
abstractText  Activated Wnt/beta-catenin signalling is a characteristic of many cancers and drives cell-cycle progression. Here, we report a mechanism linking Wnt/beta-catenin signalling to centrosome separation. We show that conductin/axin2, a negative regulator of beta-catenin, localizes at the centrosomes by binding to the centriole-associated component C-Nap1. Knockout or knockdown of conductin leads to premature centrosome separation--that is, splitting--which is abolished by knockdown of beta-catenin. Conductin promotes phosphorylation of the amino-terminal serine (Ser 33/37) and threonine (Thr 41) residues of centrosome-associated beta-catenin. Beta-catenin mutated at these residues causes centrosomal splitting, whereas a phospho-mimicking mutant of beta-catenin does not. Importantly, beta-catenin-induced splitting is not inhibited by blocking beta-catenin-dependent transcription. Treatment with Wnts and inhibition of glycogen synthase kinase 3 block beta-catenin phosphorylation and induce centrosomal splitting. These data indicate that Wnt/beta-catenin signalling and conductin regulate centrosomal cohesion by altering the phosphorylation status of beta-catenin at the centrosomes.
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