TY - JOUR
T1 - Nuclear matrix metalloproteinases
T2 - Functions resemble the evolution from the intracellular to the extracellular compartment
AU - Xie, Yingqiu
AU - Mustafa, Aidana
AU - Yerzhan, Adina
AU - Merzhakupova, Dalmira
AU - Yerlan, Perizat
AU - Orakov, Askarbek N.
AU - Wang, Xiao
AU - Huang, Yi
AU - Miao, Lixia
N1 - Funding Information:
This work was supported by Kazakhstan-China collaboration and China-Kazakhstan international grant to YX (CK-07-09) and LM (CK-07-09). This work was also supported by the grant from National Science Foundation of China to LM (No. 31672311). We thank Ayan A Nurkesh, Aisulu Maipas, Damir Oralov, Amina Amanzhanova, Gulzhaina Nusserova, Gauhar Anuar, Aizhan Meyerbekova and Anuar Zhanapiya for pre-proof reading of the manuscript.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
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U2 - 10.1038/cddiscovery.2017.36
DO - 10.1038/cddiscovery.2017.36
M3 - Review article
AN - SCOPUS:85041100283
VL - 3
JO - Cell Death Discovery
JF - Cell Death Discovery
SN - 2058-7716
M1 - 17036
ER -