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Chemoproteomic strategy identified p120-catenin glutathionylation regulates E-cadherin degradation and cell migration
Journal article   Open access

Chemoproteomic strategy identified p120-catenin glutathionylation regulates E-cadherin degradation and cell migration

Dhanushika S K Kukulage, Maheeshi Yapa Abeywardana, Nadee N J Matarage Don, Ren-Ming Hu, Kyosuke Shishikura, Megan L Matthews and Young-Hoon Ahn
Cell chemical biology, v 30(12), p1542
21 Dec 2023
PMID: 37714153
url
https://doi.org/10.1016/j.chembiol.2023.08.004View
Published, Version of Record (VoR)Open Access (Publisher-Specific) Open

Abstract

Cadherins - metabolism Catenins - metabolism Cell Movement Delta Catenin Glucose Humans Proteomics
Identification of cysteines with high oxidation susceptibility is important for understanding redox-mediated biological processes. In this report, we report a chemical proteomic strategy that finds cysteines with high susceptibility to S-glutathionylation. Our proteomic strategy, named clickable glutathione-based isotope-coded affinity tag (G-ICAT), identified 1,518 glutathionylated cysteines while determining their relative levels of glutathionylated and reduced forms upon adding hydrogen peroxide. Among identified cysteines, we demonstrated that CTNND1 (p120) C692 has high susceptibility to glutathionylation. Also, p120 wild type (WT), compared to C692S, induces its dissociation from E-cadherin under oxidative stress, such as glucose depletion. p120 and E-cadherin dissociation correlated with E-cadherin destabilization via its proteasomal degradation. Lastly, we showed that p120 WT, compared to C692S, increases migration and invasion of MCF7 cells under glucose depletion, supporting a model that p120 C692 glutathionylation increases cell migration and invasion by destabilization of E-cadherin, a core player in cell-cell adhesion.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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