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Characterization of the Proprotein Convertase-Mediated Processing of Peroxidasin and Peroxidasin-like Protein

Peroxidasin (PXDN) and peroxidasin-like protein (PXDNL) are members of the peroxidase-cyclooxygenase superfamily. PXDN functions in basement membrane synthesis by forming collagen IV crosslinks, while the function of PXDNL remains practically unknown. In this work, we characterized the post-translat...

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Autores principales: Kovács, Hajnal A., Lázár, Enikő, Várady, György, Sirokmány, Gábor, Geiszt, Miklós
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533639/
https://www.ncbi.nlm.nih.gov/pubmed/34679700
http://dx.doi.org/10.3390/antiox10101565
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author Kovács, Hajnal A.
Lázár, Enikő
Várady, György
Sirokmány, Gábor
Geiszt, Miklós
author_facet Kovács, Hajnal A.
Lázár, Enikő
Várady, György
Sirokmány, Gábor
Geiszt, Miklós
author_sort Kovács, Hajnal A.
collection PubMed
description Peroxidasin (PXDN) and peroxidasin-like protein (PXDNL) are members of the peroxidase-cyclooxygenase superfamily. PXDN functions in basement membrane synthesis by forming collagen IV crosslinks, while the function of PXDNL remains practically unknown. In this work, we characterized the post-translational proteolytic processing of PXDN and PXDNL. Using a novel knock-in mouse model, we demonstrate that the proteolytic cleavage of PXDN occurs in vivo. With the help of furin-specific siRNA we also demonstrate that the proprotein-convertase, furin participates in the proteolytic processing of PXDN. Furthermore, we demonstrate that only the proteolytically processed PXDN integrates into the extracellular matrix, highlighting the importance of the proteolysis step in PXDN’s collagen IV-crosslinking activity. We also provide multiple lines of evidence for the importance of peroxidase activity in the proteolytic processing of PXDN. Finally, we show that PXDNL does not undergo proteolytic processing, despite containing sequence elements efficiently recognized by proprotein convertases. Collectively, our observations suggest a previously unknown protein quality control during PXDN synthesis and the importance of the peroxidase activity of PXDN in this process.
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spelling pubmed-85336392021-10-23 Characterization of the Proprotein Convertase-Mediated Processing of Peroxidasin and Peroxidasin-like Protein Kovács, Hajnal A. Lázár, Enikő Várady, György Sirokmány, Gábor Geiszt, Miklós Antioxidants (Basel) Article Peroxidasin (PXDN) and peroxidasin-like protein (PXDNL) are members of the peroxidase-cyclooxygenase superfamily. PXDN functions in basement membrane synthesis by forming collagen IV crosslinks, while the function of PXDNL remains practically unknown. In this work, we characterized the post-translational proteolytic processing of PXDN and PXDNL. Using a novel knock-in mouse model, we demonstrate that the proteolytic cleavage of PXDN occurs in vivo. With the help of furin-specific siRNA we also demonstrate that the proprotein-convertase, furin participates in the proteolytic processing of PXDN. Furthermore, we demonstrate that only the proteolytically processed PXDN integrates into the extracellular matrix, highlighting the importance of the proteolysis step in PXDN’s collagen IV-crosslinking activity. We also provide multiple lines of evidence for the importance of peroxidase activity in the proteolytic processing of PXDN. Finally, we show that PXDNL does not undergo proteolytic processing, despite containing sequence elements efficiently recognized by proprotein convertases. Collectively, our observations suggest a previously unknown protein quality control during PXDN synthesis and the importance of the peroxidase activity of PXDN in this process. MDPI 2021-09-30 /pmc/articles/PMC8533639/ /pubmed/34679700 http://dx.doi.org/10.3390/antiox10101565 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kovács, Hajnal A.
Lázár, Enikő
Várady, György
Sirokmány, Gábor
Geiszt, Miklós
Characterization of the Proprotein Convertase-Mediated Processing of Peroxidasin and Peroxidasin-like Protein
title Characterization of the Proprotein Convertase-Mediated Processing of Peroxidasin and Peroxidasin-like Protein
title_full Characterization of the Proprotein Convertase-Mediated Processing of Peroxidasin and Peroxidasin-like Protein
title_fullStr Characterization of the Proprotein Convertase-Mediated Processing of Peroxidasin and Peroxidasin-like Protein
title_full_unstemmed Characterization of the Proprotein Convertase-Mediated Processing of Peroxidasin and Peroxidasin-like Protein
title_short Characterization of the Proprotein Convertase-Mediated Processing of Peroxidasin and Peroxidasin-like Protein
title_sort characterization of the proprotein convertase-mediated processing of peroxidasin and peroxidasin-like protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8533639/
https://www.ncbi.nlm.nih.gov/pubmed/34679700
http://dx.doi.org/10.3390/antiox10101565
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