PIPKI? targets to the centrosome and restrains centriole duplication.

ABSTRACT: Centriole biogenesis depends on the polo-like kinase (PLK4) and a small group of structural proteins. The spatiotemporal regulation of these proteins at pre-existing centrioles is essential to ensure that centriole duplication occurs once per cell cycle. Here, we report that phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C, hereafter referred to as PIPKI?) plays an important role in centriole fidelity. PIPKI? localized in a ring-like pattern in the intermediate pericentriolar materials around the proximal end of the centriole in G1, S and G2 phases, but not in M phase. This localization was dependent upon an association with centrosomal protein of 152 KDa (CEP152). Without detaining cells in S or M phase, the depletion of PIPKI? led to centriole amplification in a manner that was dependent upon PLK4 and spindle assembly abnormal protein 6 homolog (SAS6). The expression of exogenous PIPKI? reduced centriole amplification that occurred as a result of endogenous PIPKI? depletion, hydroxyurea treatment or PLK4 overexpression, suggesting that PIPKI? is likely to function at the PLK4 level to restrain centriole duplication. Importantly, we found that PIPKI? bound to the cryptic polo-box domain of PLK4 and that this binding reduced the kinase activity of PLK4. Together, our findings suggest that PIPKI? is a novel negative regulator of centriole duplication, which acts by modulating the homeostasis of PLK4 activity.

SUBMITTER: Xu Q 

PROVIDER: S-EPMC3953817 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other