| Autor: |
Hadjihannas MV; Nikolaus Fiebiger Center for Molecular Medicine, University Erlangen-Nürnberg, Glueckstrasse 6, Erlangen 91054, Germany., Brückner M, Behrens J |
| Jazyk: |
angličtina |
| Zdroj: |
EMBO reports [EMBO Rep] 2010 Apr; Vol. 11 (4), pp. 317-24. Date of Electronic Publication: 2010 Mar 19. |
| DOI: |
10.1038/embor.2010.23 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Plný text