Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation

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  • dc.contributor.author Villanueva Cañas, José Luis, 1984-
  • dc.contributor.author Fernández Fuentes, Narcís
  • dc.contributor.author Saul, Dominik
  • dc.contributor.author Kosinsky, Robyn Laura
  • dc.contributor.author Teyssier, Catherine
  • dc.contributor.author Rogalska, Malgorzata
  • dc.contributor.author Pegenaute Pérez, Ferran
  • dc.contributor.author Oliva Miguel, Baldomero
  • dc.contributor.author Notredame, Cedric
  • dc.contributor.author Beato, Miguel
  • dc.contributor.author Sharma, Priyanka
  • dc.date.accessioned 2024-06-07T06:14:58Z
  • dc.date.available 2024-06-07T06:14:58Z
  • dc.date.issued 2024
  • dc.description.abstract Peptidyl arginine deiminases (PADIs) catalyze protein citrullination, a post-translational conversion of arginine to citrulline. The most widely expressed member of this family, PADI2, regulates cellular processes that impact several diseases. We hypothesized that we could gain new insights into PADI2 function through a systematic evolutionary and structural analysis. Here, we identify 20 positively selected PADI2 residues, 16 of which are structurally exposed and maintain PADI2 interactions with cognate proteins. Many of these selected residues reside in non-catalytic regions of PADI2. We validate the importance of a prominent loop in the middle domain that encompasses PADI2 L162, a residue under positive selection. This site is essential for interaction with the transcription elongation factor (P-TEFb) and mediates the active transcription of the oncogenes c-MYC, and CCNB1, as well as impacting cellular proliferation. These insights could be key to understanding and addressing the role of the PADI2 c-MYC axis in cancer progression.
  • dc.description.sponsorship This work was supported by grants to P.S. from the French National Research Agency (ANR) Young Investigator grant (ANR-21-CE12-0010), French Cancer Research Foundation (ARCPJA22021050003683), La Ligue Foundation for Cancer, France (Haute-Garonne, 285458), National Institute of Health and Medical Research (INSERM) Young Recruitment Support (U1194SHA), Cancéropôle Grand Sud-Ouest collaboration grant (R21031FF), Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier, Toulouse, France. This work was also supported by a grant to M.B. from the European Research Council Synergy Grant “4DGenome” (609989).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Villanueva-Cañas JL, Fernandez-Fuentes N, Saul D, Kosinsky RL, Teyssier C, Rogalska ME, et al. Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation. iScience. 2024 Mar 27;27(4):109584. DOI: 10.1016/j.isci.2024.109584
  • dc.identifier.doi http://dx.doi.org/10.1016/j.isci.2024.109584
  • dc.identifier.issn 2589-0042
  • dc.identifier.uri http://hdl.handle.net/10230/60383
  • dc.language.iso eng
  • dc.publisher Elsevier
  • dc.relation.ispartof iScience. 2024 Mar 27;27(4):109584
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/609989
  • dc.rights © 2024 Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.keyword Biochemistry
  • dc.subject.keyword Bioinformatics
  • dc.subject.keyword Biological sciences
  • dc.subject.keyword Evolutionary biology
  • dc.subject.keyword Molecular biology
  • dc.subject.keyword Natural sciences
  • dc.title Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion