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Tumor suppressor activity of profilin requires a functional actin binding site

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Item Type:Article
Title:Tumor suppressor activity of profilin requires a functional actin binding site
Creators Name:Wittenmayer, N. and Jandrig, B. and Rothkegel, M. and Schlueter, K. and Arnold, W. and Haensch, W. and Scherneck, S. and Jockusch, B.M.
Abstract:Profilin 1 (PFN1) is a regulator of the microfilament system and is involved in various signaling pathways. It interacts with many cytoplasmic and nuclear ligands. The importance of PFN1 for human tissue differentiation has been demonstrated by the findings that human cancer cells, expressing conspicuously low PFN1 levels, adopt a nontumorigenic phenotype upon raising their PFN1 level. In the present study, we characterize the ligand binding site crucial for profilin's tumor suppressor activity. Starting with CAL51, a human breast cancer cell line highly tumorigenic in nude mice, we established stable clones that express PFN1 mutants differentially defective in ligand binding. Clones expressing PFN1 mutants with reduced binding to either poly-proline-stretch ligands or phosphatidyl-inositol-4,5-bisphosphate, but with a functional actin binding site, were normal in growth, adhesion, and anchorage dependence, with only a weak tendency to elicit tumors in nude mice, similar to controls expressing wild-type PFN1. In contrast, clones expressing a mutant with severely reduced capacity to bind actin still behaved like the parental CAL51 and were highly tumorigenic. We conclude that the actin binding site on profilin is instrumental for normal differentiation of human epithelia and the tumor suppressor function of PFN1.
Keywords:Actins, Binding Sites, Cell Adhesion, Cell Division, Tumor Cell Line, Cell Movement, Collagen, Contractile Proteins, Cytoplasm, Drug Combinations, Epithelium, Tumor Suppressor Genes, Immunoblotting, Laminin, Ligands, Microfilament Proteins, Microfilaments, Mutation, Neoplasm Transplantation, Neoplasms, Phenotype, Phosphatidylinositol 4,5-Diphosphate, Point Mutation, Profilins, Proteoglycans, Recombinant Proteins, Signal Transduction, Time Factors, Transfection, Animals, Mice, Nude Mice
Source:Molecular Biology of the Cell
Publisher:American Society for Cell Biology
Page Range:1600-1608
Date:April 2004
Additional Information:Copyright (c) 2004 by The American Society for Cell Biology
Official Publication:https://doi.org/10.1091/mbc.E03-12-0873
PubMed:View item in PubMed

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