Membrane type-1 matrix metalloproteinase (MT1-MMP) exhibits an important intracellular cleavage function and causes chromosome instability

Vladislav S. Golubkov, Sarah Boyd, Alexei Y. Savinov, Alexei V. Chekanov, Andrei L. Osterman, Albert Remacle, Dmitri V. Rozanov, Stephen J. Doxsey, Alex Y. Strongin

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Elevated expression of membrane type-1 matrix metalloproteinase (MT1-MMP) is closely associated with malignancies. There is a consensus among scientists that cell surface-associated MT1-MMP is a key player in pericellular proteolytic events. Now we have identified an intracellular, hitherto unknown, function of MT1-MMP. We demonstrated that MT1-MMP is trafficked along the tubulin cytoskeleton. A fraction of cellular MT1-MMP accumulates in the centrosomal compartment. MT1-MMP targets an integral centrosomal protein, pericentrin. Pericentrin is known to be essential to the normal functioning of centrosomes and to mitotic spindle formation. Expression of MT1-MMP stimulates mitotic spindle aberrations and aneuploidy in non-malignant cells. Volumes of data indicate that chromosome instability is an early event of carcinogenesis. In agreement, the presence of MT1-MMP activity correlates with degraded pericentrin in tumor biopsies, whereas normal tissues exhibit intact pericentrin. We believe that our data show a novel proteolytic pathway to chromatin instability and elucidate the close association of MT1-MMP with malignant transformation.

Original languageEnglish (US)
Pages (from-to)25079-25086
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number26
DOIs
StatePublished - Jul 1 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Golubkov, V. S., Boyd, S., Savinov, A. Y., Chekanov, A. V., Osterman, A. L., Remacle, A., Rozanov, D. V., Doxsey, S. J., & Strongin, A. Y. (2005). Membrane type-1 matrix metalloproteinase (MT1-MMP) exhibits an important intracellular cleavage function and causes chromosome instability. Journal of Biological Chemistry, 280(26), 25079-25086. https://doi.org/10.1074/jbc.M502779200