Nuclear matrix metalloproteinases: Functions resemble the evolution from the intracellular to the extracellular compartment

Yingqiu Xie, Aidana Mustafa, Adina Yerzhan, Dalmira Merzhakupova, Perizat Yerlan, Askarbek N. Orakov, Xiao Wang, Yi Huang, Lixia Miao

Research output: Contribution to journalReview article

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number17036
JournalCell Death Discovery
Volume3
DOIs
Publication statusPublished - Jan 1 2017

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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    Xie, Y., Mustafa, A., Yerzhan, A., Merzhakupova, D., Yerlan, P., Orakov, A. N., Wang, X., Huang, Y., & Miao, L. (2017). Nuclear matrix metalloproteinases: Functions resemble the evolution from the intracellular to the extracellular compartment. Cell Death Discovery, 3, [17036]. https://doi.org/10.1038/cddiscovery.2017.36