Literature DB >> 28041906

APC/CFzr/Cdh1-Dependent Regulation of Planar Cell Polarity Establishment via Nek2 Kinase Acting on Dishevelled.

Ursula Weber1, Marek Mlodzik2.   

Abstract

The Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase, well known for its role in cell-cycle progression. However, it has been linked to additional functions, mainly in neuronal contexts, when using the co-activator Cdh1/Fzr. Here, our data indicate a post-mitotic requirement for the APC/CFzr/Cdh1 in epithelial cell patterning and planar cell polarity (PCP) in Drosophila. PCP signaling is critical for development by establishing cellular asymmetries and orientation within the plane of an epithelium, via differential localization of distinct complexes of core PCP factors. Loss of APC/C function leads to reduced levels of Dishevelled (Dsh), a core PCP factor. The effect of APC/C on Dsh is mediated by Nek2 kinase, which can phosphorylate Dsh and is a direct APC/CFzr/Cdh1 substrate. We have thus uncovered a pathway of regulation whereby APC/CFzr/Cdh1 negatively regulates Nek2, which negatively regulates Dsh, to ensure its proper stoichiometric requirement and localization during PCP establishment.
Copyright © 2017 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  Drosophila; Nek2 kinase; anaphase-promoting complex; asymmetric protein localization; planar cell polarity; post-mitotic function; proteasome-mediated degradation

Mesh：

Substances：

Year:  2016        PMID： 28041906      PMCID： PMC5225046          DOI： 10.1016/j.devcel.2016.12.006

Source DB:  PubMed          Journal:  Dev Cell        ISSN： 1534-5807            Impact factor:   12.270


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