Studies on Cadherin/Catenin Complexes

Project: Research project

Description

DESCRIPTION (provided by applicant): The majority of human cancers are cancers of epithelial tissues called carcinomas. It is common for metastases to be a major contributor to the morbidity and mortality associated with carcinomas. In order for cells to leave the primary tumor and migrate to distant sites, it is thought they must modulate their ability to recognize neighboring cells. Proteins of the cadherin family are major components of the cell-cell recognition machinery. Cadherins are transmembrane proteins that cluster at sites of cell-cell adhesion called adherens junctions. The cadherin most common to epithelial tissues is E-cadherin. During the process of epithelial-to- mesenchymal transition, the function of E-cadherin is frequently down regulated. Sometimes this is caused by decreased synthesis of the mRNA or protein. In other cases, the function of E-cadherin can be lost without significant change in expression. A critical regulator of E-cadherin function is the protein called p120-catenin. Palmitoylation is a reversible post-translational modification that can significantly change how proteins interact with membranes. We have found that p120-catenin is palmitoylated at a single cysteine residue. In the studies described here, we propose identifying the enzymes that add palmitate to p120-catenin and the enzymes that remove it. Knowing the enzymes involved may offer methods of altering E-cadherin function by altering the palmitoylation status of p120-catenin. We also propose studies in model systems to further our understanding how the palmitoylation of p120-catenin affects the biochemistry and cell biology of E-cadherin-mediated cell- cell adhesion. Our long term goal is to determine if modulating this aspect of p120-catenin can be used to prevent or treat metastases.
StatusFinished
Effective start/end date7/1/146/30/16

Funding

  • National Institutes of Health: $75,250.00
  • National Institutes of Health: $75,250.00

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Catenins
Cadherins
Lipoylation
Cell Adhesion
Proteins
Enzymes
Epithelium
Neoplasm Metastasis
Carcinoma
Adherens Junctions
Neoplasms
Epithelial-Mesenchymal Transition
Palmitates
Cellular Structures
Post Translational Protein Processing
Biochemistry
Cysteine
Cell Biology
delta catenin
Morbidity

ASJC

  • Medicine(all)