O-glycosylation regulates autolysis of cellular membrane type-1 matrix metalloproteinase (MT1-MMP).

The Journal of Biological Chemistry
Albert RemacleAlex Y Strongin

Abstract

MT1-MMP is a key enzyme in cancer cell invasion and metastasis. The activity of cellular MT1-MMP is regulated by furin-like proprotein convertases, TIMPs, shedding, autoproteolysis, dimerization, exocytosis, endocytosis, and recycling. Our data demonstrate that, in addition to these already known mechanisms, MT1-MMP is regulated by O-glycosylation of its hinge region. Insignificant autolytic degradation is characteristic for naturally expressed, glycosylated, MT1-MMP. In turn, extensive autolytic degradation, which leads to the inactivation of the protease and the generation of its C-terminal membrane-tethered degraded species, is a feature of overexpressed MT1-MMP. We have determined that incomplete glycosylation stimulates extensive autocatalytic degradation and self-inactivation of MT1-MMP. Self-proteolysis commences during the secretory process of MT1-MMP through the cell compartment to the plasma membrane. The strongly negatively charged sialic acid is the most important functional moiety of the glycopart of MT1-MMP. We hypothesize that sialic acid of the O-glycosylation cassette restricts the access of the catalytic domain to the hinge region and to the autolytic cleavage site and protects MT1-MMP from autolysis. Overall,...Continue Reading

References

Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·F JeanG Thomas
Apr 6, 1999·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·G MurphyJ Gavrilovic
Jul 27, 1999·The Journal of Biological Chemistry·H Nagase, J F Woessner
Jul 11, 2000·Molecular Biology of the Cell·I Yana, S J Weiss
Feb 15, 2001·The Biochemical Journal·B AnnabiR Béliveau
Aug 23, 2001·Proceedings of the National Academy of Sciences of the United States of America·D E BassiA J Klein-Szanto
Nov 8, 2001·Proceedings of the National Academy of Sciences of the United States of America·A JiangD Pei
May 7, 2002·Nature Reviews. Cancer·Mikala Egeblad, Zena Werb
May 25, 2002·Seminars in Cancer Biology·Sonia Hernandez-BarrantesRafael Fridman
May 29, 2002·Proceedings of the National Academy of Sciences of the United States of America·Ekaterina MorgunovaKarl Tryggvason
Sep 17, 2002·Current Opinion in Cell Biology·Motoharu Seiki
Oct 3, 2002·Nature Reviews. Molecular Cell Biology·Gary Thomas
Oct 12, 2002·Glycoconjugate Journal·H Rüdiger, H J Gabius
Dec 14, 2002·Laboratory Investigation; a Journal of Technical Methods and Pathology·Stanley ZuckerJian Cao
Dec 18, 2002·Bioorganic Chemistry·Lakshmi P KotraShahriar Mobashery
Apr 2, 2003·The Biochemical Journal·Erik MaquoiFrancis Frankenne
Apr 17, 2003·Current Topics in Developmental Biology·Stanley ZuckerCarlos Lopez-Otin
May 15, 2003·Molecular Biotechnology·F Xavier Gomis-Rüth
Dec 13, 2003·The Journal of Biological Chemistry·Yi I WuM Sharon Stack
Feb 5, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Akihiro KatayamaYasuaki Harabuchi
May 12, 2004·Journal of Cellular Physiology·Pamela OsenkowskiRafael Fridman
Jul 16, 2004·American Journal of Physiology. Cell Physiology·Teresa M BuckWilliam R Skach

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Citations

Mar 19, 2013·The International Journal of Biochemistry & Cell Biology·H M SchröderT Ludwig
Mar 24, 2010·The Journal of Biological Chemistry·Ilian A RadichevAlex Y Strongin
Dec 12, 2012·The European Journal of Neuroscience·David TongeJohn Pizzey
Jun 25, 2009·International Journal of Cancer. Journal International Du Cancer·Nor Eddine SounniAlex Y Strongin
May 31, 2015·Journal of Muscle Research and Cell Motility·C Snyman, C U Niesler
Apr 25, 2013·Antiviral Research·Antonella PasquatoStefan Kunz
Apr 14, 2010·Circulation·Begoña LópezJavier Díez
Apr 30, 2016·The Journal of Biological Chemistry·Ieva BagdonaiteHans H Wandall
Jun 25, 2020·International Journal of Molecular Sciences·Katherine FalkowskiTomasz Kantyka
Mar 20, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Irina G LuzinaSergei P Atamas
Jan 1, 2021·International Journal of Molecular Sciences·Stephan Niland, Johannes A Eble
Jul 7, 2021·Neoplasia : an International Journal for Oncology Research·Saya OzakiJunya Tanaka
Jul 10, 2021·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Natalia MorachoCristina Sánchez-Camacho
Aug 5, 2021·The FEBS Journal·Hans H WandallIeva Bagdonaite
Jul 24, 2021·Journal of Molecular Cell Biology·Xiao-Dan XiaDa-Wei Zhang

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