| First Author | Borgal L | Year | 2016 |
| Journal | Cell Cycle | Volume | 15 |
| Issue | 8 | Pages | 1034-45 |
| PubMed ID | 26919559 | Mgi Jnum | J:382078 |
| Mgi Id | MGI:8310336 | Doi | 10.1080/15384101.2016.1152429 |
| Citation | Borgal L, et al. (2016) Jade-1S phosphorylation induced by CK1alpha contributes to cell cycle progression. Cell Cycle 15(8):1034-45 |
| abstractText | The PHD zinc finger protein Jade-1S is a component of the HBO1 histone acetyltransferase complex and binds chromatin in a cell cycle-dependent manner. Jade-1S also acts as an E3 ubiquitin ligase for the canonical Wnt effector protein beta-catenin and is influenced by CK1alpha-mediated phosphorylation. To further elucidate the functional impact of this phosphorylation, we used a stable, low-level expression system to express either wild-type or mutant Jade-1S lacking the N-terminal CK1alpha phosphorylation motif. Interactome analyses revealed that the Jade-1S mutant unable to be phosphorylated by CK1alpha has an increased binding affinity to proteins involved in chromatin remodelling, histone deacetylation, transcriptional repression, and ribosome biogenesis. Interestingly, cells expressing the mutant displayed an elongated cell shape and a delay in cell cycle progression. Finally, phosphoproteomic analyses allowed identification of a Jade-1S site phosphorylated in the presence of CK1alpha but closely resembling a PLK1 phosphorylation motif. Our data suggest that Jade-1S phosphorylation at an N-terminal CK1alpha motif creates a PLK1 phospho-binding domain. We propose CK1alpha phosphorylation of Jade 1S to serve as a molecular switch, turning off chromatin remodelling functions of Jade-1S and allowing timely cell cycle progression. As Jade-1S protein expression in the kidney is altered upon renal injury, this could contribute to understanding mechanisms underlying epithelial injury repair. |
