Title:Molecular Mechanisms Regulating Matrix Metalloproteinases
Volume: 12
Issue: 10
Author(s): Christina Piperi and Athanasios G. Papavassiliou
Affiliation:
Keywords:
Matrix metalloproteinases, gene expression, epigenetics, microRNA, mutation, polymorphisms, multidomain enzymes, zinc-dependent
activity, zymogen activation, molecular mechanisms, gene transcription, epigenetic modifications, nucleotide polymorphisms, cellular homeostasis
Abstract: The family of matrix metalloproteinases (MMPs) comprises 24 multidomain enzymes with a zinc-dependent
activity. Their structural diversity over the archetypal domain organization confers variable biological function to these
molecules ranging from cellular homeostasis and control of tissue turnover to implication in multiple pathological conditions
such as inflammation, arthritis, cardiovascular disease and cancer. MMP expression and activity exhibits high tissuespecies-
and signal-specificity and involves multiple regulatory mechanisms that co-ordinate zymogen activation, endogenous
inhibition and gene transcription. In this article, we provide an overview of the molecular mechanisms that regulate
MMPs gene expression at transcriptional and post-transcriptional level through integration of signals from multiple pathways
to cis-acting elements present in MMP promoters, epigenetic modifications, mRNA stability mechanisms and microRNA
modulation. Loss of MMP activity through mutations and single nucleotide polymorphisms is further discussed
in the context of disease susceptibility.