000151021 001__ 151021
000151021 005__ 20251017144622.0
000151021 0247_ $$2doi$$a10.1016/j.abb.2022.109125
000151021 0248_ $$2sideral$$a128385
000151021 037__ $$aART-2022-128385
000151021 041__ $$aeng
000151021 100__ $$aNeira, José L.
000151021 245__ $$aBiochemical and biophysical characterization of PADI4 supports its involvement in cancer
000151021 260__ $$c2022
000151021 5060_ $$aAccess copy available to the general public$$fUnrestricted
000151021 5203_ $$aPADI4 (protein-arginine deiminase, also known as protein L-arginine iminohydrolase) is one of the human isoforms of a family of Ca2+-dependent proteins catalyzing the conversion of arginine to citrulline. Although the consequences of this process, known as citrullination, are not fully understood, all PADIs have been suggested to play essential roles in development and cell differentiation. They have been found in a wide range of cells and tissues and, among them, PADI4 is present in macrophages, monocytes, granulocytes and cancer cells. In this work, we focused on the biophysical features of PADI4 and, more importantly, how its expression was altered in cancer cells. Firstly, we described the different expression patterns of PADI4 in various cancer cell lines and its colocalization with the tumor-related protein p53. Secondly, we carried out a biophysical characterization of PADI4, by using a combination of biophysical techniques and in silico molecular dynamics simulations. Our biochemical results suggest the presence of several forms of PADI4 with different subcellular localizations, depending on the cancer cell line. Furthermore, PADI4 could have a major role in tumorigenesis by regulating p53 expression in certain cancer cell lines. On the other hand, the native structure of PADI4 was strongly pH-dependent both in the absence or presence of Ca2+, and showed two pH-titrations at basic and acidic pH values. Thus, there was a narrow pH range (from 6.5 to 8.0) where the protein was dimeric and had a native structure, supporting its role in histones citrullination. Thermal denaturations were always two-state, but guanidinium-induced ones showed that PADI4 unfolded through at least one intermediate. Our simulation results suggest that the thermal melting of PADI4 structure was rather homogenous throughout its sequence. The overall results are discussed in terms of the functional role of PADI4 in the development of cancer.
000151021 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-20R$$9info:eu-repo/grantAgreement/ES/DGA/E45-20R$$9info:eu-repo/grantAgreement/ES/ISCIII-ERDF-ESF/PI18-00349-Investing in your future$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/BFU2016-78232-P$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/RTI2018-097991-B-I00$$9info:eu-repo/grantAgreement/ES/MINECO/CP19-00095
000151021 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
000151021 590__ $$a3.9$$b2022
000151021 591__ $$aBIOPHYSICS$$b17 / 70 = 0.243$$c2022$$dQ1$$eT1
000151021 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b126 / 285 = 0.442$$c2022$$dQ2$$eT2
000151021 592__ $$a0.867$$b2022
000151021 593__ $$aBiophysics$$c2022$$dQ1
000151021 593__ $$aMolecular Biology$$c2022$$dQ2
000151021 593__ $$aBiochemistry$$c2022$$dQ2
000151021 594__ $$a7.5$$b2022
000151021 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000151021 700__ $$aAraujo-Abad, Salomé
000151021 700__ $$aCámara-Artigas, Ana
000151021 700__ $$aRizzuti, Bruno
000151021 700__ $$0(orcid)0000-0001-5664-1729$$aAbian, Olga$$uUniversidad de Zaragoza
000151021 700__ $$aGiudici, Ana Marcela
000151021 700__ $$0(orcid)0000-0001-5702-4538$$aVelazquez-Campoy, Adrián$$uUniversidad de Zaragoza
000151021 700__ $$aJuan Romero, Camino de
000151021 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000151021 773__ $$g717 (2022), 109125 [16 pp.]$$pArch. biochem. biophys.$$tARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS$$x0003-9861
000151021 8564_ $$s2825199$$uhttps://zaguan.unizar.es/record/151021/files/texto_completo.pdf$$yVersión publicada
000151021 8564_ $$s2451183$$uhttps://zaguan.unizar.es/record/151021/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000151021 909CO $$ooai:zaguan.unizar.es:151021$$particulos$$pdriver
000151021 951__ $$a2025-10-17-14:22:11
000151021 980__ $$aARTICLE