HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 51, 42237-42241, December 23, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/51/42237    most recent M510139200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Golubkov, V. S. Articles by Strongin, A. Y. Search for Related Content PubMed PubMed Citation Articles by Golubkov, V. S. Articles by Strongin, A. Y. Social Bookmarking                      What's this?

Centrosomal Pericentrin Is a Direct Cleavage Target of Membrane Type-1 Matrix Metalloproteinase in Humans but Not in Mice

POTENTIAL IMPLICATIONS FOR TUMORIGENESIS^*

Vladislav S. Golubkov, Alexei V. Chekanov, Stephen J. Doxsey, and Alex Y. Strongin1

From the Cancer Research Center, The Burnham Institute for Medical Research, La Jolla, California 92037 and the University of Massachusetts Medical School, Worcester, Massachusetts 01605

Membrane type-1 matrix metalloproteinase (MT1-MMP) exhibits distinctive and important pericellular cleavage functions. Recently, we determined that MT1-MMP was trafficked to the centrosomes in the course of endocytosis. Our data suggested that the functionally important, integral, centrosomal protein, pericentrin-2, was a cleavage target of MT1-MMP in human and in canine cells and that the sequence of the cleavage sites were ALRRLLG¹¹⁵⁶L¹¹⁵⁷FG and ALRRLLS²⁰⁶⁸L²⁰⁶⁹FG, respectively. The presence of Asp-948 at the P1 position inactivated the corresponding site (ALRRLLD⁹⁴⁸-L⁹⁴⁹FGD) in murine pericentrin. To confirm that MT1-MMP itself cleaves pericentrin directly, rather than indirectly, we analyzed the cleavage of the peptides that span the MT1-MMP cleavage site. In addition, we analyzed glioma U251 cells, which co-expressed MT1-MMP with the wild type murine pericentrin and the D948G mutant. We determined that the D948G mutant that exhibited the cleavage sequence of human pericentrin was sensitive to MT1-MMP, whereas unmodified murine pericentrin was resistant to proteolysis. Taken together, our results confirm that MT1-MMP cleaves pericentrin-2 in humans but not in mice and that mouse models of cancer probably cannot be used to critically examine MT1-MMP functionality.

Received for publication, September 15, 2005 , and in revised form, October 24, 2005.

^* This work was supported by National Institutes of Health Grants CA83017, CA77470, and RR020843 (to A. Y. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: The Burnham Institute, 10901 North Torrey Pines Rd., La Jolla, CA. Tel.: 858-713-6271; Fax: 858-713-9925; E-mail: strongin{at}burnham.org.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. V. Chernov, N. E. Sounni, A. G. Remacle, and A. Y. Strongin Epigenetic Control of the Invasion-promoting MT1-MMP/MMP-2/TIMP-2 Axis in Cancer Cells J. Biol. Chem., May 8, 2009; 284(19): 12727 - 12734. [Abstract] [Full Text] [PDF]

				J. Kim, Y.-L. Choi, A. Vallentin, B. S. Hunrichs, M. K. Hellerstein, D. M. Peehl, and D. Mochly-Rosen Centrosomal PKC{beta}II and Pericentrin Are Critical for Human Prostate Cancer Growth and Angiogenesis Cancer Res., August 15, 2008; 68(16): 6831 - 6839. [Abstract] [Full Text] [PDF]

				V. W.M. van Hinsbergh and P. Koolwijk Endothelial sprouting and angiogenesis: matrix metalloproteinases in the lead Cardiovasc Res, May 1, 2008; 78(2): 203 - 212. [Abstract] [Full Text] [PDF]

				J. E. Sillibourne, B. Delaval, S. Redick, M. Sinha, and S. J. Doxsey Chromatin Remodeling Proteins Interact with Pericentrin to Regulate Centrosome Integrity Mol. Biol. Cell, September 1, 2007; 18(9): 3667 - 3680. [Abstract] [Full Text] [PDF]

				V. S. Golubkov, A. V. Chekanov, A. Y. Savinov, D. V. Rozanov, N. V. Golubkova, and A. Y. Strongin Membrane Type-1 Matrix Metalloproteinase Confers Aneuploidy and Tumorigenicity on Mammary Epithelial Cells Cancer Res., November 1, 2006; 66(21): 10460 - 10465. [Abstract] [Full Text] [PDF]

				D. M. Hockenbery MMPs in Unusual Places Am. J. Pathol., October 1, 2006; 169(4): 1101 - 1103. [Full Text] [PDF]