tailieunhanh - Báo cáo khoa học: Regulation of matrix metalloproteinase activity in health and disease

The activity of matrix metalloproteinases (MMPs) is regulated at several levels, including enzyme activation, inhibition, complex formation and compartmentalization. Regulation at the transcriptional level is also impor-tant, although this is not a subject of the present minireview. | 1FEBS Journal MINIREVIEW Regulation of matrix metalloproteinase activity in health and disease Elin Hadler-Olsen Bodil Fadnes Ingebrigt Sylte Lars Uhlin-Hansen and Jan-Olof Winberg Department of MedicalBiology Faculty of Health Sciences University of Tromso Norway Keywords activation compartmentalization complexes exosite heteromers inhibition matrix metalloproteinases Correspondence . Winberg Department of Medical Biology Faculty of Health Sciences University of Tromso 9037 Tromso Norway Fax 47 77 64 53 50 Tel 47 77 64 54 88 E-mail Received 30 April 2010 revised 4 October 2010 accepted 18 October 2010 doi The activity of matrix metalloproteinases MMPs is regulated at several levels including enzyme activation inhibition complex formation and compartmentalization. Regulation at the transcriptional level is also important although this is not a subject of the present minireview. Most MMPs are secreted and have their function in the extracellular environment. This is also the case for the membrane-type MMPs MT-MMPs . MMPs are also found inside cells both in the nucleus cytosol and organelles. The role of intracellular located MMPs is still poorly understood although recent studies have unraveled some of their functions. The localization activation and activity of MMPs are regulated by their interactions with other proteins proteoglycan core proteins and or their glycosaminoglycan chains as well as other molecules. Complexes formed between MMPs and various molecules may also include interactions with noncatalytic sites. Such exosites are regions involved in substrate processing localized outside the active site and are potential binding sites of specific MMP inhibitors. Knowledge about regulation of MMP activity is essential for understanding various physiological processes and pathogenesis of diseases as well as for the development of new MMP targeting drugs. Introduction Matrix metalloproteinases MMPs are a .

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