Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis. - Laboratoire Jean-Alexandre Dieudonné Accéder directement au contenu
Article Dans Une Revue American Journal of Pathology Année : 2006

Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis.

Karim Si-Tayeb
Arnaud Monvoisin
Marion Decossas
  • Fonction : Auteur

Résumé

Matrix metalloproteinase (MMP)-3 is a protease involved in cancer progression and tissue remodeling. Using immunofluorescence and immunoelectron microscopy, we identified nuclear localization of MMP-3 in several cultured cell types and in human liver tissue sections. Western blot analysis of nuclear extracts revealed two immunoreactive forms of MMP-3 at 35 and 45 kd, with the 35-kd form exhibiting caseinolytic activity. By transient transfection, we expressed active MMP-3 fused to the enhanced green fluorescent protein (EGFP/aMMP-3) in Chinese hamster ovary cells. We showed that EGFP/aMMP-3 translocates into the nucleus. A functional nuclear localization signal was demonstrated by the loss of nuclear translocation after site-directed mutagenesis of a putative nuclear localization signal and by the ability of the MMP-3 nuclear localization signal to drive a heterologous protein into the nucleus. Finally, expression by Chinese hamster ovary cells of EGFP/aMMP-3 induced a twofold increase of apoptosis rate, compared with EGFP/pro-MMP-3, which does not translocate to the nucleus. Increased apoptosis was abolished by site-directed mutagenesis of the catalytic site of MMP-3 or by using the MMP inhibitor GM6001. This study elucidates for the first time the mechanisms of nuclear localization of a MMP and shows that nuclear MMP-3 can induce apoptosis via its catalytic activity.
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Dates et versions

hal-00215931 , version 1 (24-01-2008)

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Karim Si-Tayeb, Arnaud Monvoisin, Claire Mazzocco, Sébastien Lepreux, Marion Decossas, et al.. Matrix metalloproteinase 3 is present in the cell nucleus and is involved in apoptosis.. American Journal of Pathology, 2006, 169 (4), pp.1390-401. ⟨10.2353/ajpath.2006.060005.⟩. ⟨hal-00215931⟩
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