000118917 001__ 118917 000118917 005__ 20240319081008.0 000118917 0247_ $$2doi$$a10.3390/cells11142166 000118917 0248_ $$2sideral$$a130316 000118917 037__ $$aART-2022-130316 000118917 041__ $$aeng 000118917 100__ $$aNeira, J. L. 000118917 245__ $$aHuman enzyme PADI4 binds to the nuclear carrier Importin a3 000118917 260__ $$c2022 000118917 5060_ $$aAccess copy available to the general public$$fUnrestricted 000118917 5203_ $$aPADI4 is a peptidyl-arginine deiminase (PADI) involved in the conversion of arginine to citrulline. PADI4 is present in macrophages, monocytes, granulocytes, and several cancer cells. It is the only PADI family member observed within both the nucleus and the cytoplasm. PADI4 has a predicted nuclear localization sequence (NLS) comprising residues Pro56 to Ser83, to allow for nuclear translocation. Recent predictors also suggest that the region Arg495 to Ile526 is a possible NLS. To understand how PADI4 is involved in cancer, we studied the ability of intact PADI4 to bind importin a3 (Impa3), a nuclear transport factor that plays tumor-promoting roles in several cancers, and its truncated species (¿Impa3) without the importin-binding domain (IBB), by using fluorescence, circular dichroism (CD), and isothermal titration calorimetry (ITC). Furthermore, the binding of two peptides, encompassing the first and the second NLS regions, was also studied using the same methods and molecular docking simulations. PADI4 interacted with both importin species, with affinity constants of ~1–5 µM. The isolated peptides also interacted with both importins. The molecular simulations predict that the anchoring of both peptides takes place in the major binding site of Impa3 for the NLS of cargo proteins. These findings suggest that both NLS regions were essentially responsible for the binding of PADI4 to the two importin species. Our data are discussed within the framework of a cell mechanism of nuclear transport that is crucial in cancer. 000118917 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-20R$$9info:eu-repo/grantAgreement/ES/DGA/E45-20R$$9info:eu-repo/grantAgreement/ES/ISCIII/PI18-0394$$9info:eu-repo/grantAgreement/ES/MCIU-AEI-FEDER/RTI2018-097991-B-I00$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P$$9info:eu-repo/grantAgreement/ES/MINECO/CP19-00095 000118917 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000118917 590__ $$a6.0$$b2022 000118917 592__ $$a1.537$$b2022 000118917 591__ $$aCELL BIOLOGY$$b60 / 191 = 0.314$$c2022$$dQ2$$eT1 000118917 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2022$$dQ1 000118917 594__ $$a9.0$$b2022 000118917 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000118917 700__ $$aRizzuti, B. 000118917 700__ $$0(orcid)0000-0001-5664-1729$$aAbián, O.$$uUniversidad de Zaragoza 000118917 700__ $$aAraujo-Abad, S. 000118917 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza 000118917 700__ $$aJuan Romero, C. de 000118917 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole. 000118917 773__ $$g11, 14 (2022), 2166 [28 pp.]$$pCells$$tCells$$x2073-4409 000118917 8564_ $$s2626334$$uhttps://zaguan.unizar.es/record/118917/files/texto_completo.pdf$$yVersión publicada 000118917 8564_ $$s2550105$$uhttps://zaguan.unizar.es/record/118917/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000118917 909CO $$ooai:zaguan.unizar.es:118917$$particulos$$pdriver 000118917 951__ $$a2024-03-18-14:49:05 000118917 980__ $$aARTICLE