Post-translational modification-dependent activity of matrix metalloproteinases

Elizabeta Madzharova, Philipp Kastl, Fabio Sabino, Ulrich auf dem Keller*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Due to their capacity to process different proteins of the extracellular matrix (ECM), matrix metalloproteinases (MMPs) were initially described as a family of secreted proteases, functioning as main ECM regulators. However, through proteolytic processing of various biomolecules, MMPs also modulate intra- and extracellular pathways and networks. Thereby, they are functionally implicated in the regulation of multiple physiological and pathological processes. Consequently, MMP activity is tightly regulated through a combination of epigenetic, transcriptional, and post-transcriptional control of gene expression, proteolytic activation, post-translational modifications (PTMs), and extracellular inhibition. In addition, MMPs, their substrates and ECM binding partners are frequently modified by PTMs, which suggests an important role of PTMs in modulating the pleiotropic activities of these proteases. This review summarizes the recent progress towards understanding the role of PTMs (glycosylation, phosphorylation, glycosaminoglycans) on the activity of several members of the MMP family.

Original languageEnglish
Article number3077
JournalInternational Journal of Molecular Sciences
Volume20
Issue number12
Number of pages18
ISSN1661-6596
DOIs
Publication statusPublished - 2019

Keywords

  • Glycosaminoglycans
  • Glycosylation
  • MMPs
  • Phosphorylation
  • PTMs

Cite this

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title = "Post-translational modification-dependent activity of matrix metalloproteinases",
abstract = "Due to their capacity to process different proteins of the extracellular matrix (ECM), matrix metalloproteinases (MMPs) were initially described as a family of secreted proteases, functioning as main ECM regulators. However, through proteolytic processing of various biomolecules, MMPs also modulate intra- and extracellular pathways and networks. Thereby, they are functionally implicated in the regulation of multiple physiological and pathological processes. Consequently, MMP activity is tightly regulated through a combination of epigenetic, transcriptional, and post-transcriptional control of gene expression, proteolytic activation, post-translational modifications (PTMs), and extracellular inhibition. In addition, MMPs, their substrates and ECM binding partners are frequently modified by PTMs, which suggests an important role of PTMs in modulating the pleiotropic activities of these proteases. This review summarizes the recent progress towards understanding the role of PTMs (glycosylation, phosphorylation, glycosaminoglycans) on the activity of several members of the MMP family.",
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author = "Elizabeta Madzharova and Philipp Kastl and Fabio Sabino and {auf dem Keller}, Ulrich",
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doi = "10.3390/ijms20123077",
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Post-translational modification-dependent activity of matrix metalloproteinases. / Madzharova, Elizabeta; Kastl, Philipp; Sabino, Fabio; auf dem Keller, Ulrich.

In: International Journal of Molecular Sciences , Vol. 20, No. 12, 3077, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Post-translational modification-dependent activity of matrix metalloproteinases

AU - Madzharova, Elizabeta

AU - Kastl, Philipp

AU - Sabino, Fabio

AU - auf dem Keller, Ulrich

PY - 2019

Y1 - 2019

N2 - Due to their capacity to process different proteins of the extracellular matrix (ECM), matrix metalloproteinases (MMPs) were initially described as a family of secreted proteases, functioning as main ECM regulators. However, through proteolytic processing of various biomolecules, MMPs also modulate intra- and extracellular pathways and networks. Thereby, they are functionally implicated in the regulation of multiple physiological and pathological processes. Consequently, MMP activity is tightly regulated through a combination of epigenetic, transcriptional, and post-transcriptional control of gene expression, proteolytic activation, post-translational modifications (PTMs), and extracellular inhibition. In addition, MMPs, their substrates and ECM binding partners are frequently modified by PTMs, which suggests an important role of PTMs in modulating the pleiotropic activities of these proteases. This review summarizes the recent progress towards understanding the role of PTMs (glycosylation, phosphorylation, glycosaminoglycans) on the activity of several members of the MMP family.

AB - Due to their capacity to process different proteins of the extracellular matrix (ECM), matrix metalloproteinases (MMPs) were initially described as a family of secreted proteases, functioning as main ECM regulators. However, through proteolytic processing of various biomolecules, MMPs also modulate intra- and extracellular pathways and networks. Thereby, they are functionally implicated in the regulation of multiple physiological and pathological processes. Consequently, MMP activity is tightly regulated through a combination of epigenetic, transcriptional, and post-transcriptional control of gene expression, proteolytic activation, post-translational modifications (PTMs), and extracellular inhibition. In addition, MMPs, their substrates and ECM binding partners are frequently modified by PTMs, which suggests an important role of PTMs in modulating the pleiotropic activities of these proteases. This review summarizes the recent progress towards understanding the role of PTMs (glycosylation, phosphorylation, glycosaminoglycans) on the activity of several members of the MMP family.

KW - Glycosaminoglycans

KW - Glycosylation

KW - MMPs

KW - Phosphorylation

KW - PTMs

U2 - 10.3390/ijms20123077

DO - 10.3390/ijms20123077

M3 - Journal article

C2 - 31238509

AN - SCOPUS:85068851904

VL - 20

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 12

M1 - 3077

ER -