000099300 001__ 99300
000099300 005__ 20230914083317.0
000099300 0247_ $$2doi$$a10.3390/cells8111453
000099300 0248_ $$2sideral$$a122815
000099300 037__ $$aART-2019-122815
000099300 041__ $$aeng
000099300 100__ $$aSantofimia-Castaño, P.
000099300 245__ $$aTargeting the Stress-Induced Protein NUPR1 to Treat Pancreatic Adenocarcinoma
000099300 260__ $$c2019
000099300 5060_ $$aAccess copy available to the general public$$fUnrestricted
000099300 5203_ $$aCancer cells activate stress-response mechanisms to adapt themselves to a variety of stressful conditions. Among these protective mechanisms, those controlled by the stress-induced nuclear protein 1 (NUPR1 ) belong to the most conserved ones. NUPR1 is an 82-residue-long, monomeric, basic and intrinsically disordered protein (IDP), which was found to be invariably overexpressed in some, if not all, cancer tissues. Remarkably, we and others have previously showed that genetic inactivation of the Nupr1 gene antagonizes the growth of pancreatic cancer as well as several other tumors. With the use of a multidisciplinary strategy by combining biophysical, biochemical, bioinformatic, and biological approaches, a trifluoperazine-derived compound, named ZZW-115, has been identified as an inhibitor of the NUPR1 functions. The anticancer activity of the ZZW-115 was first validated on a large panel of cancer cells. Furthermore, ZZW-115 produced a dose-dependent tumor regression of the tumor size in xenografted mice. Mechanistically, we have demonstrated that NUPR1 binds to several importins. Because ZZW-115 binds NUPR1 through the region around the amino acid Thr68, which is located into the nuclear location signal (NLS) region of the protein, we demonstrated that treatment with ZZW-115 inhibits completely the translocation of NUPR1 from the cytoplasm to the nucleus by competing with importins.
000099300 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B01$$9info:eu-repo/grantAgreement/ES/DGA/B89$$9info:eu-repo/grantAgreement/ES/FIS/PI15-00663$$9info:eu-repo/grantAgreement/ES/FIS/PI18-00343$$9info:eu-repo/grantAgreement/ES/ISCIII/CPII13-00017$$9info:eu-repo/grantAgreement/ES/MINECO/BFU2016-78232-P
000099300 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000099300 590__ $$a4.366$$b2019
000099300 591__ $$aCELL BIOLOGY$$b70 / 194 = 0.361$$c2019$$dQ2$$eT2
000099300 655_4 $$ainfo:eu-repo/semantics/review$$vinfo:eu-repo/semantics/publishedVersion
000099300 700__ $$aXia, Y.
000099300 700__ $$aPeng, L.
000099300 700__ $$0(orcid)0000-0001-5702-4538$$aVelázquez-Campoy, A.$$uUniversidad de Zaragoza
000099300 700__ $$0(orcid)0000-0001-5664-1729$$aAbián, O.$$uUniversidad de Zaragoza
000099300 700__ $$aLan, W.
000099300 700__ $$aLomberk, G.
000099300 700__ $$aUrrutia, R.
000099300 700__ $$aRizzuti, B.
000099300 700__ $$aSoubeyran, P.
000099300 700__ $$aNeira, J.L.
000099300 700__ $$aIovanna, J.
000099300 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000099300 773__ $$g8, 11 (2019), 1453 [9 pp]$$pCells$$tCells$$x2073-4409
000099300 8564_ $$s466031$$uhttps://zaguan.unizar.es/record/99300/files/texto_completo.pdf$$yVersión publicada
000099300 8564_ $$s2549808$$uhttps://zaguan.unizar.es/record/99300/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000099300 909CO $$ooai:zaguan.unizar.es:99300$$particulos$$pdriver
000099300 951__ $$a2023-09-13-11:01:54
000099300 980__ $$aARTICLE