Matrix Metalloproteinase 3 Is Present in the Cell Nucleus and Is Involved in Apoptosis
The American Journal of Pathology. 2006-10-01; 169(4): 1390-1401
DOI: 10.2353/ajpath.2006.060005
Lire sur PubMed
https://www.bordeaux-neurocampus.fr/12198
1. Am J Pathol. 2006 Oct;169(4):1390-401. doi: 10.2353/ajpath.2006.060005.
Matrix metalloproteinase 3 is present in the cell nucleus and is involved in
apoptosis.
Si-Tayeb K(1), Monvoisin A, Mazzocco C, Lepreux S, Decossas M, Cubel G, Taras D,
Blanc JF, Robinson DR, Rosenbaum J.
Author information:
(1)INSERM E362, Université Victor Segalen Bordeaux 2, 33076 Bordeaux, France.
Comment in
Am J Pathol. 2006 Oct;169(4):1101-3. doi: 10.2353/ajpath.2006.060553.
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.
DOI: 10.2353/ajpath.2006.060005
PMCID: PMC1780186
PMID: 17003494 [Indexed for MEDLINE]