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Cell Cycle. 2016;15(8):1034-45. doi: 10.1080/15384101.2016.1152429.

Jade-1S phosphorylation induced by CK1α contributes to cell cycle progression.

Author information

1
a Department II of Internal Medicine ; University of Cologne ; Cologne , Germany.
2
b Center for Molecular Medicine Cologne (CMMC); University of Cologne ; Cologne , Germany.
3
c Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne ; Cologne , Germany.
4
d Department I of Internal Medicine ; University of Cologne ; Cologne , Germany.
5
e Systems Biology of Ageing Cologne; University of Cologne ; Cologne , Germany.

Abstract

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 β-catenin and is influenced by CK1α-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 CK1α phosphorylation motif. Interactome analyses revealed that the Jade-1S mutant unable to be phosphorylated by CK1α 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 CK1α but closely resembling a PLK1 phosphorylation motif. Our data suggest that Jade-1S phosphorylation at an N-terminal CK1α motif creates a PLK1 phospho-binding domain. We propose CK1α 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.

KEYWORDS:

CK1α; Cell cycle; Jade-1S; NuRD complex; PLK1; S-phase; mitosis; proliferation

PMID:
26919559
PMCID:
PMC4889251
[Available on 2017-02-26]
DOI:
10.1080/15384101.2016.1152429
[Indexed for MEDLINE]
Free PMC Article

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