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. |