PXD026238

PXD026238 is an original dataset announced via ProteomeXchange.

Title	PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis
Description	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 (PADIPADs), including PADIPAD1-4. 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 PADIPAD2 citrullinated FBLN5 preferentially in young lungs compared to adult lungs. Genetic ablation of PADIPAD2 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 PADIPAD activity. Our data uncover a novel function of citrullination, namely promoting elastogenesis, and provide additional insights to how elastogenesis is regulated.
HostingRepository	PRIDE
AnnounceDate	2021-07-22
AnnouncementXML	Submission_2021-07-22_08:19:26.614.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Paul Thompson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2021-05-24 21:56:33	ID requested
⏵ 1	2021-07-22 08:19:27	announced

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, 102():70-84(2021) [pubmed]

submitter keyword: citrullination, deimination, deiminase, elastic fiber, Fibulin-5, lung compliance

Paul Thompson
contact affiliation	Univeristy of Massachusetts Medical School Department of Biochemistry and Molecular Pharmacology
contact email	paul.thompson@umassmed.edu
lab head
Paul Thompson
contact affiliation	Univeristy of Massachusetts Medical School
contact email	paul.thompson@umassmed.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/07/PXD026238

PRIDE project URI

• PRIDE
  1. PXD026238
     1. Label: PRIDE project
     2. Name: PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis