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dc.contributor.authorSun, Bo
dc.contributor.authorTomita, Beverly
dc.contributor.authorSalinger, Ari J.
dc.contributor.authorTilvawala, Ronak
dc.contributor.authorLi, Ling
dc.contributor.authorHakami, Hana
dc.contributor.authorLiu, Tao
dc.contributor.authorTsoyi, Konstantin
dc.contributor.authorRosas, Ivan O.
dc.contributor.authorReinhardt, Dieter P.
dc.contributor.authorThompson, Paul R
dc.contributor.authorHo, I-Cheng
dc.date2022-08-11T08:08:28.000
dc.date.accessioned2022-08-23T15:56:17Z
dc.date.available2022-08-23T15:56:17Z
dc.date.issued2021-08-01
dc.date.submitted2022-01-02
dc.identifier.citation<p>Sun B, Tomita B, Salinger A, Tilvawala RR, Li L, Hakami H, Liu T, Tsoyi K, Rosas IO, Reinhardt DP, Thompson PR, Ho IC. PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis. Matrix Biol. 2021 Aug;102:70-84. doi: 10.1016/j.matbio.2021.07.001. Epub 2021 Jul 15. PMID: 34274450; PMCID: PMC8502204. <a href="https://doi.org/10.1016/j.matbio.2021.07.001">Link to article on publisher's site</a></p>
dc.identifier.issn0945-053X (Linking)
dc.identifier.doi10.1016/j.matbio.2021.07.001
dc.identifier.pmid34274450
dc.identifier.urihttp://hdl.handle.net/20.500.14038/29934
dc.description.abstractThe formation of elastic fibers is active only in the perinatal period. How elastogenesis is developmentally regulated is not fully understood. Citrullination is a unique form of post-translational modification catalyzed by peptidylarginine deiminases (PADs), including PAD1-4. Its physiological role is largely unknown. By using an unbiased proteomic approach of lung tissues, we discovered that FBLN5 and LTBP4, two key elastogenic proteins, were temporally modified in mouse and human lungs. We further demonstrated that PAD2 citrullinated FBLN5 preferentially in young lungs compared to adult lungs. Genetic ablation of PAD2 resulted in attenuated elastogenesis in vitro and age-dependent emphysema in vivo. Mechanistically, citrullination protected FBLN5 from proteolysis and subsequent inactivation of its elastogenic activity. Furthermore, citrullinated but not native FBLN5 partially rescued in vitro elastogenesis in the absence of PAD activity. Our data uncover a novel function of citrullination, namely promoting elastogenesis, and provide additional insights to how elastogenesis is regulated.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=34274450&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1016/j.matbio.2021.07.001
dc.subjectCitrullination
dc.subjectDeiminase
dc.subjectDeimination
dc.subjectElastic fiber
dc.subjectEmphysema
dc.subjectFibulin-5
dc.subjectLung compliance
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectChemical and Pharmacologic Phenomena
dc.subjectEnzymes and Coenzymes
dc.titlePAD2-mediated citrullination of Fibulin-5 promotes elastogenesis
dc.typeJournal Article
dc.source.journaltitleMatrix biology : journal of the International Society for Matrix Biology
dc.source.volume102
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/2137
dc.identifier.contextkey27074128
html.description.abstract<p>The formation of elastic fibers is active only in the perinatal period. How elastogenesis is developmentally regulated is not fully understood. Citrullination is a unique form of post-translational modification catalyzed by peptidylarginine deiminases (PADs), including PAD1-4. Its physiological role is largely unknown. By using an unbiased proteomic approach of lung tissues, we discovered that FBLN5 and LTBP4, two key elastogenic proteins, were temporally modified in mouse and human lungs. We further demonstrated that PAD2 citrullinated FBLN5 preferentially in young lungs compared to adult lungs. Genetic ablation of PAD2 resulted in attenuated elastogenesis in vitro and age-dependent emphysema in vivo. Mechanistically, citrullination protected FBLN5 from proteolysis and subsequent inactivation of its elastogenic activity. Furthermore, citrullinated but not native FBLN5 partially rescued in vitro elastogenesis in the absence of PAD activity. Our data uncover a novel function of citrullination, namely promoting elastogenesis, and provide additional insights to how elastogenesis is regulated.</p>
dc.identifier.submissionpathfaculty_pubs/2137
dc.contributor.departmentThompson Lab
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.source.pages70-84


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