Universität zu Köln

Borgal, Lori, Rinschen, Markus M., Dafinger, Claudia, Liebrecht, Valerie I., Abken, Hinrich, Benzing, Thomas and Schermer, Bernhard ORCID: 0000-0002-5194-9000 (2016). Jade-1S phosphorylation induced by CK1 alpha contributes to cell cycle progression. Cell Cycle, 15 (8). S. 1034 - 1046. PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 1551-4005

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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 beta-catenin and is influenced by CK1 alpha-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 CK1 alpha phosphorylation motif. Interactome analyses revealed that the Jade-1S mutant unable to be phosphorylated by CK1 alpha 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 CK1 alpha but closely resembling a PLK1 phosphorylation motif. Our data suggest that Jade-1S phosphorylation at an N-terminal CK1 alpha motif creates a PLK1 phospho-binding domain. We propose CK1 alpha 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Borgal, Lori UNSPECIFIED UNSPECIFIED UNSPECIFIED Rinschen, Markus M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dafinger, Claudia UNSPECIFIED UNSPECIFIED UNSPECIFIED Liebrecht, Valerie I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-290171
DOI:	10.1080/15384101.2016.1152429
Journal or Publication Title:	Cell Cycle
Volume:	15
Number:	8
Page Range:	S. 1034 - 1046
Date:	2016
Publisher:	TAYLOR & FRANCIS INC
Place of Publication:	PHILADELPHIA
ISSN:	1551-4005
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language POLO-LIKE KINASE-1; WNT REGULATOR JADE-1; EPITHELIAL-CELLS; BETA-CATENIN; TUMOR-SUPPRESSOR; PROTEIN-KINASE; HAT HBO1; PLK1; CHROMATIN; KIDNEY Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/29017