Universität zu Köln

Borgal, Lori, Rinschen, Markus M., Dafinger, Claudia, Hoff, Sylvia, Reinert, Matthaeus J., Lamkemeyer, Tobias, Lienkamp, Soeren S., Benzing, Thomas and Schermer, Bernhard ORCID: 0000-0002-5194-9000 (2014). Casein Kinase 1 alpha Phosphorylates the Wnt Regulator Jade-1 and Modulates Its Activity. J. Biol. Chem., 289 (38). S. 26344 - 26357. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1083-351X

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Abstract

Tight regulation of Wnt/beta-catenin signaling is critical for vertebrate development and tissue maintenance, and deregulation can lead to a host of disease phenotypes, including developmental disorders and cancer. Proteins associated with primary cilia and centrosomes have been demonstrated to negatively regulate canonical Wnt signaling in interphase cells. The plant homeodomain zinc finger protein Jade-1 can act as an E3 ubiquitin ligase-targeting beta-catenin for proteasomal degradation and concentrates at the centrosome and ciliary basal body in addition to the nucleus in interphase cells. We demonstrate that the destruction complex component casein kinase 1 beta(CK1 alpha) phosphorylates Jade-1 at a conserved SLS motif and reduces the ability of Jade-1 to inhibit beta-catenin signaling. Consistently, Jade-1 lacking the SLS motif is more effective than wild-type Jade-1 in reducing beta-catenin-induced secondary axis formation in Xenopus laevis embryos in vivo. Interestingly, CK1 alpha also phosphorylates beta-catenin and the destruction complex component adenomatous polyposis coli at a similar SLS motif to the effect that beta-catenin is targeted for degradation. The opposing effect of Jade-1 phosphorylation by CK1 alpha suggests a novel example of the dual functions of CK1 alpha activity to either oppose or promote canonical Wnt signaling in a context-dependent manner.

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 Hoff, Sylvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinert, Matthaeus J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lamkemeyer, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Lienkamp, Soeren S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Benzing, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Schermer, Bernhard UNSPECIFIED orcid.org/0000-0002-5194-9000 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-428551
DOI:	10.1074/jbc.M114.562165
Journal or Publication Title:	J. Biol. Chem.
Volume:	289
Number:	38
Page Range:	S. 26344 - 26357
Date:	2014
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1083-351X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BETA-CATENIN DEGRADATION; NEGATIVE REGULATOR; SIGNALING PATHWAY; EPITHELIAL-CELLS; PROTEIN-KINASE; STEM-CELLS; DISEASE; REPAIR; CK1; QUANTIFICATION Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/42855