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Minus end–directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions
The adherens junction (AJ) plays a crucial role in maintaining cell–cell adhesion in epithelial tissues. Previous studies show that KIFC3, a minus end–directed kinesin motor, moves into AJs via microtubules that grow from clusters of CAMSAP3 (also known as Nezha), a protein that binds microtubule mi...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244195/ https://www.ncbi.nlm.nih.gov/pubmed/25253721 http://dx.doi.org/10.1091/mbc.E14-07-1245 |
Sumario: | The adherens junction (AJ) plays a crucial role in maintaining cell–cell adhesion in epithelial tissues. Previous studies show that KIFC3, a minus end–directed kinesin motor, moves into AJs via microtubules that grow from clusters of CAMSAP3 (also known as Nezha), a protein that binds microtubule minus ends. The function of junction-associated KIFC3, however, remains to be elucidated. Here we find that KIFC3 binds the ubiquitin-specific protease USP47, a protease that removes ubiquitin chains from substrates and hence inhibits proteasome-mediated proteolysis, and recruits it to AJs. Depletion of KIFC3 or USP47 promotes cleavage of E-cadherin at a juxtamembrane region of the cytoplasmic domain, resulting in the production of a 90-kDa fragment and the internalization of E-cadherin. This cleavage depends on the E3 ubiquitin protein ligase Hakai and is inhibited by proteasome inhibitors. E-cadherin ubiquitination consistently increases after depletion of KIFC3 or USP47. These findings suggest that KIFC3 suppresses the ubiquitination and resultant degradation of E-cadherin by recruiting USP47 to AJs, a process that may be involved in maintaining stable cell–cell adhesion in epithelial sheets. |
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