000127816 001__ 127816
000127816 005__ 20240731103412.0
000127816 0247_ $$2doi$$a10.1016/j.ijbiomac.2023.125632
000127816 0248_ $$2sideral$$a134869
000127816 037__ $$aART-2023-134869
000127816 041__ $$aeng
000127816 100__ $$aAraujo-Abad, Salomé
000127816 245__ $$aThe intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells
000127816 260__ $$c2023
000127816 5060_ $$aAccess copy available to the general public$$fUnrestricted
000127816 5203_ $$aRYBP (Ring1 and YY 1 binding protein) is a multifunctional, intrinsically disordered protein (IDP), best described as a transcriptional regulator. It exhibits a ubiquitin-binding functionality, binds to other transcription factors, and has a key role during embryonic development. RYBP, which folds upon binding to DNA, has a Zn-finger domain at its N-terminal region. By contrast, PADI4 is a well-folded protein and it is one the human isoforms of a family of enzymes implicated in the conversion of arginine to citrulline. As both proteins intervene in signaling pathways related to cancer development and are found in the same localizations within the cell, we hypothesized they may interact. We observed their association in the nucleus and cytosol in several cancer cell lines, by using immunofluorescence (IF) and proximity ligation assays (PLAs). Binding also occurred in vitro, as measured by isothermal titration calorimetry (ITC) and fluorescence, with a low micromolar affinity (~1 μM). AlphaFold2-multimer (AF2) results indicate that PADI4's catalytic domain interacts with the Arg53 of RYBP docking into its active site. As RYBP sensitizes cells to PARP (Poly (ADP-ribose) polymerase) inhibitors, we applied them in combination with an enzymatic inhibitor of PADI4 observing a change in cell proliferation, and the hampering of the interaction of both proteins. This study unveils for the first time the possible citrullination of an IDP, and suggests that this new interaction, whether it involves or not citrullination of RYBP, might have implications in cancer development and progression.
000127816 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-20R$$9info:eu-repo/grantAgreement/ES/DGA/E45-20R$$9info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI21-00394$$9info:eu-repo/grantAgreement/ES/ISCIII/PI22-00824$$9info:eu-repo/grantAgreement/ES/MICINN/AEI/PID2021-127296OB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PDC2022-133952-I00$$9info:eu-repo/grantAgreement/ES/MINECO/CP19-00095
000127816 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000127816 590__ $$a7.7$$b2023
000127816 592__ $$a1.245$$b2023
000127816 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b34 / 313 = 0.109$$c2023$$dQ1$$eT1
000127816 593__ $$aBiochemistry$$c2023$$dQ1
000127816 591__ $$aPOLYMER SCIENCE$$b6 / 94 = 0.064$$c2023$$dQ1$$eT1
000127816 593__ $$aStructural Biology$$c2023$$dQ2
000127816 591__ $$aCHEMISTRY, APPLIED$$b6 / 74 = 0.081$$c2023$$dQ1$$eT1
000127816 593__ $$aMolecular Biology$$c2023$$dQ2
000127816 594__ $$a13.7$$b2023
000127816 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000127816 700__ $$aFuentes-Baile, María
000127816 700__ $$aRizzuti, Bruno
000127816 700__ $$aBazán, J. Fernando
000127816 700__ $$aVillamarin-Ortiz, Adrián
000127816 700__ $$aSaceda, Miguel
000127816 700__ $$aFernández, Eduardo
000127816 700__ $$aVidal, Miguel
000127816 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, Olga$$uUniversidad de Zaragoza
000127816 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, Adrián$$uUniversidad de Zaragoza
000127816 700__ $$aJuan Romero, Camino de
000127816 700__ $$0(orcid)0000-0003-0668-977X$$aNeira, José L.$$uUniversidad de Zaragoza
000127816 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000127816 7102_ $$15007$$2570$$aUniversidad de Zaragoza$$bDpto. Informát.Ingenie.Sistms.$$cÁrea Lenguajes y Sistemas Inf.
000127816 773__ $$g246 (2023), 125632 [14 pp.]$$pInt. j. biol. macromol.$$tInternational journal of biological macromolecules$$x0141-8130
000127816 8564_ $$s20868958$$uhttps://zaguan.unizar.es/record/127816/files/texto_completo.pdf$$yVersión publicada
000127816 8564_ $$s2270348$$uhttps://zaguan.unizar.es/record/127816/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000127816 909CO $$ooai:zaguan.unizar.es:127816$$particulos$$pdriver
000127816 951__ $$a2024-07-31-10:04:42
000127816 980__ $$aARTICLE