Mannello Ferdinando, Medda Virginia
Department of Biomolecular Sciences, Section of Clinical Biochemistry, Unit of Cell Biology, University Carlo Bo of Urbino, Via O. Ubaldini 7, 61029 Urbino (PU), Italy.
Prog Histochem Cytochem. 2012 Mar;47(1):27-58. doi: 10.1016/j.proghi.2011.12.002. Epub 2012 Jan 5.
Matrix metalloproteinases (MMPs) were originally identified as matrixin proteases that act in the extracellular matrix. Recent works have uncovered nontraditional roles for MMPs in the extracellular space as well as in the cytosol and nucleus. There is strong evidence that subspecialized and compartmentalized matrixins participate in many physiological and pathological cellular processes, in which they can act as both degradative and regulatory proteases. In this review, we discuss the transcriptional and translational control of matrixin expression, their regulation of intracellular sorting, and the structural basis of activation and inhibition. In particular, we highlight the emerging roles of various matrixin forms in diseases. The activity of matrix metalloproteinases is regulated at several levels, including enzyme activation, inhibition, complex formation and compartmentalization. Most MMPs are secreted and have their function in the extracellular environment. 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.
基质金属蛋白酶（MMPs）最初被鉴定为作用于细胞外基质的基质蛋白酶。最近的研究发现，MMPs在细胞外空间以及细胞质和细胞核中具有非传统作用。有强有力的证据表明，亚专业化和区室化的基质蛋白酶参与许多生理和病理细胞过程，在这些过程中它们既可以作为降解性蛋白酶，也可以作为调节性蛋白酶。在本综述中，我们讨论了基质蛋白酶表达的转录和翻译控制、它们对细胞内分选的调节以及激活和抑制的结构基础。特别地，我们强调了各种基质蛋白酶形式在疾病中的新作用。基质金属蛋白酶的活性在多个水平受到调节，包括酶的激活、抑制、复合物形成和区室化。大多数MMPs是分泌型的，在细胞外环境中发挥作用。MMPs也存在于细胞内，包括细胞核、细胞质和细胞器中。尽管最近的研究揭示了细胞内MMPs的一些功能，但它们的作用仍知之甚少。MMPs的定位、激活和活性受其与其他蛋白质、蛋白聚糖核心蛋白和/或其糖胺聚糖链以及其他分子的相互作用调节。MMPs与各种分子形成的复合物也可能包括与非催化位点的相互作用。这种外位点是参与底物加工的区域，位于活性位点之外，是特定MMP抑制剂的潜在结合位点。了解MMP活性的调节对于理解各种生理过程和疾病发病机制以及开发新的MMP靶向药物至关重要。
