Matrix metalloproteinase (MMP) is defined as an endopeptidase in the extracellular matrix (ECM), which plays essential roles in physiological processes such as organogenesis, wound healing, angiogenesis, apoptosis and motility. MMPs are produced and assembled in the cytoplasm as proenzymes with a cytoplasmic domain and require extracellular activation. MMPs can degrade receptors, extracellular matrix proteins, PARPs and release apoptotic substances. MMPs have been found in the cytosol, organelles and extracellular compartments and recently many types of MMPs have been found in the nucleus. However, the mechanisms and roles of MMPs inside the cell nucleus are still poorly understood. Here we summarized the nuclear localization mechanisms of MMPs and their functions in the nucleus such as apoptosis, tissue remodeling upon injury and cancer progression. Most importantly, we found that nuclear MMPs have evolved to translocate to membrane and target ECM possibly through evolution of nuclear localization signal (NLS), natural selection and anti-apoptotic survival. Thus, the knowledge about the evolution and regulation of nuclear MMPs appears to be essential in understanding a variety of cellular processes along with the development of MMP-targeted therapeutic drugs against the progression of certain diseases.

中文翻译：

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核基质金属蛋白酶：功能类似于从细胞内到细胞外区室的演变。

基质金属蛋白酶（MMP）被定义为细胞外基质（ECM）中的一种内肽酶，在诸如器官发生，伤口愈合，血管生成，细胞凋亡和运动性等生理过程中起着至关重要的作用。MMP作为具有细胞质结构域的酶在细胞质中产生和组装，并需要细胞外激活。MMPs可以降解受体，细胞外基质蛋白，PARPs并释放凋亡物质。在细胞质，细胞器和细胞外区室中发现了MMP，最近在细胞核中发现了许多类型的MMP。但是，细胞核内MMP的机制和作用仍知之甚少。在这里，我们总结了MMP的核定位机制及其在细胞核中的功能，例如凋亡，损伤和癌症进展时组织重塑。最重要的是，我们发现核MMPs可能已经通过核定位信号（NLS），自然选择和抗凋亡存活的进化而转移到膜和靶向ECM。因此，关于核MMPs的进化和调控的知识似乎对于理解多种细胞过程以及针对某些疾病进展的针对MMP的治疗药物的开发至关重要。