000095753 001__ 95753
000095753 005__ 20230706131408.0
000095753 0247_ $$2doi$$a10.1172/jci.insight.138117
000095753 0248_ $$2sideral$$a120191
000095753 037__ $$aART-2020-120191
000095753 041__ $$aeng
000095753 100__ $$aLan, W.
000095753 245__ $$aZZW-115-dependent inhibition of NUPR1 nuclear translocation sensitizes cancer cells to genotoxic agents
000095753 260__ $$c2020
000095753 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095753 5203_ $$aEstablishing the interactome of the cancer-associated stress protein Nuclear Protein 1 (NUPR1), we found that it binds to several hundreds of proteins, including proteins involved in nuclear translocation, DNA repair, and key factors of the SUMO pathway. We demonstrated that the NUPR1 inhibitor ZZW-115, an organic synthetic molecule, competes with importins for the binding to the NLS region of NUPR1, thereby inhibiting its nuclear translocation. We hypothesized, and then proved, that inhibition of NUPR1 by ZZW-115 sensitizes cancer cells to DNA damage induced by several genotoxic agents. Strikingly, we found that treatment with ZZW-115 reduced SUMOylation of several proteins involved in DNA damage response (DDR). We further report that the presence of recombinant NUPR1 improved the SUMOylation in a cell-free system, indicating that NUPR1 directly stimulates the SUMOylation machinery. We propose that ZZW-115 sensitizes cancer cells to genotoxic agents by inhibiting the nuclear translocation of NUPR1 and thereby decreasing the SUMOylation-dependent functions of key proteins involved in the DDR.
000095753 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B25-17R$$9info:eu-repo/grantAgreement/ES/DGA/E45-17R$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00663$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017$$9info:eu-repo/grantAgreement/ES/ISCIII-FIS-ERDF-ESF/PI18-00343$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P
000095753 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000095753 590__ $$a8.315$$b2020
000095753 591__ $$aMEDICINE, RESEARCH & EXPERIMENTAL$$b16 / 140 = 0.114$$c2020$$dQ1$$eT1
000095753 592__ $$a4.099$$b2020
000095753 593__ $$aMedicine (miscellaneous)$$c2020$$dQ1
000095753 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095753 700__ $$aSantofimia-Castaño, P.
000095753 700__ $$aSwayden, M.
000095753 700__ $$aXia, Y.
000095753 700__ $$aZhou, Z.
000095753 700__ $$aAudebert, S.
000095753 700__ $$aCamoin, L.
000095753 700__ $$aHuang, C.
000095753 700__ $$aPeng, L.
000095753 700__ $$0(orcid)0000-0003-4726-7821$$aJiménez-Alesanco, A.$$uUniversidad de Zaragoza
000095753 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000095753 700__ $$aAbián, O.
000095753 700__ $$aLomberk, G.
000095753 700__ $$aUrrutia, R.
000095753 700__ $$aRizzuti, B.
000095753 700__ $$aGeli, V.
000095753 700__ $$aSoubeyran, P.
000095753 700__ $$aNeira, J.L.
000095753 700__ $$aIovanna, J.
000095753 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000095753 773__ $$g5, 18 (2020), e138117 [19 pp]$$pJCI insight$$tJCI insight$$x2379-3708
000095753 8564_ $$s833371$$uhttps://zaguan.unizar.es/record/95753/files/texto_completo.pdf$$yVersión publicada
000095753 8564_ $$s116911$$uhttps://zaguan.unizar.es/record/95753/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095753 909CO $$ooai:zaguan.unizar.es:95753$$particulos$$pdriver
000095753 951__ $$a2023-07-06-12:20:44
000095753 980__ $$aARTICLE