A Mediator of Rho-dependent Invasion Moonlights as a Methionine Salvage Enzyme
RhoA controls changes in cell morphology and invasion associated with cancer phenotypes. Cell lines derived from melanoma tumors at varying stages revealed that RhoA is selectively activated in cells of metastatic origin. We describe a functional proteomics strategy to identify proteins regulated by...
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Published in | Molecular & cellular proteomics Vol. 8; no. 10; pp. 2308 - 2320 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Elsevier Inc
01.10.2009
American Society for Biochemistry and Molecular Biology The American Society for Biochemistry and Molecular Biology |
Subjects | |
Online Access | Get full text |
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Summary: | RhoA controls changes in cell morphology and invasion associated with cancer phenotypes. Cell lines derived from melanoma tumors at varying stages revealed that RhoA is selectively activated in cells of metastatic origin. We describe a functional proteomics strategy to identify proteins regulated by RhoA and report a previously uncharacterized human protein, named “mediator of RhoA-dependent invasion (MRDI),” that is induced in metastatic cells by constitutive RhoA activation and promotes cell invasion. In human melanomas, MRDI localization correlated with stage, showing nuclear localization in nevi and early stage tumors and cytoplasmic localization with plasma membrane accentuation in late stage tumors. Consistent with its role in promoting cell invasion, MRDI localized to cell protrusions and leading edge membranes in cultured cells and was required for cell motility, tyrosine phosphorylation of focal adhesion kinase, and modulation of actin stress fibers. Unexpectedly MRDI had enzymatic function as an isomerase that converts the S-adenosylmethionine catabolite 5-methylribose 1-phosphate into 5-methylribulose 1-phosphate. The enzymatic function of MRDI was required for methionine salvage from S-adenosylmethionine but distinct from its function in cell invasion. Thus, mechanisms used by signal transduction pathways to control cell movement have evolved from proteins with ancient function in amino acid metabolism. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 f Present address: Orion Pharma, Orionintiel, P.O. Box 65, FI-02101 Espoo, Finland. d Present address: OSI Pharmaceuticals Inc., 1 Bioscience Park Dr., Farmingdale, NY 11735. Deceased January 8, 2009. b Present address: Division of Applied Biochemistry, Dept. of Bioproductive Science, Utsunomiya University, Tochigi 321-8505, Japan. |
ISSN: | 1535-9476 1535-9484 |
DOI: | 10.1074/mcp.M900178-MCP200 |