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Biochemistry Research International
Volume 2011, Article ID 630319, 12 pages
http://dx.doi.org/10.1155/2011/630319
Research Article

Furin Functions as a Nonproteolytic Chaperone for Matrix Metalloproteinase-28: MMP-28 Propeptide Sequence Requirement

1Divsions of Cancer Prevention, Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
2Division Hematology and Oncology, Department of Medicine, Stony Brook University, Stony Brook, NY 11794, USA
3Department of Research, Veterans Affairs Medical Center, Northport, NY 11768, USA
4Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA

Received 27 June 2010; Revised 16 September 2010; Accepted 27 September 2010

Academic Editor: Sanford I. Bernstein

Copyright © 2011 Maria Pavlaki et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Although MMP-28 is involved in numerous important physiologic and pathologic conditions, the mechanisms of action of this secreted proteinase is not well understood. We now have demonstrated that furin serves as an intermolecular chaperone for MMP-28 secretion by interacting with the propeptide domain of MMP-28. Employing COS-1 cells transfected with MMP-28 cDNA, protein levels of MMP-28 were quite low in conditioned media as compared to cell lysates. Coexpression of MMP-28 with furin cDNA resulted in markedly enhanced MMP-28 secretion. Contrary to expectation, cleavage of MMP-28 at the furin consensus sequence did not occur and proteolytic inactive furin was equally effective in enhancing MMP-28 secretion. Furin and MMP-28 coimmunoprecipitated and were partially coimmunolocalized in the cytoplasm of transfected cells. Cotransfection with furin cDNA also enhanced MMP-28 induced cell migration. In conclusion, our data provide a novel mechanism for MMP-28 function in cells in which furin serves as an intermolecular chaperone.