000079636 001__ 79636
000079636 005__ 20200716101446.0
000079636 0247_ $$2doi$$a10.3390/cancers11040444
000079636 0248_ $$2sideral$$a112239
000079636 037__ $$aART-2019-112239
000079636 041__ $$aeng
000079636 100__ $$0(orcid)0000-0003-2156-8378$$aNaval, Javier$$uUniversidad de Zaragoza
000079636 245__ $$aImportance of TRAIL molecular anatomy in receptor oligomerization and signaling. Implications for cancer therapy
000079636 260__ $$c2019
000079636 5060_ $$aAccess copy available to the general public$$fUnrestricted
000079636 5203_ $$a(TNF)-related apoptosis-inducing ligand (TRAIL) is able to activate the extrinsic apoptotic pathway upon binding to DR4/TRAIL-R1 and/or DR5/TRAIL-R2 receptors. Structural data indicate that TRAIL functions as a trimer that can engage three receptor molecules simultaneously, resulting in receptor trimerization and leading to conformational changes in TRAIL receptors. However, receptor conformational changes induced by the binding of TRAIL depend on the molecular form of this death ligand, and not always properly trigger the apoptotic cascade. In fact, TRAIL exhibits a much stronger pro-apoptotic activity when is found as a transmembrane protein than when it occurs as a soluble form and this enhanced biological activity is directly linked to its ability to cluster TRAIL receptors in supra-molecular structures. In this regard, cells involved in tumor immunosurveillance, such as activated human T cells, secrete endogenous TRAIL as a transmembrane protein associated with lipid microvesicles called exosomes upon T-cell reactivation. Consequently, it seems clear that a proper oligomerization of TRAIL receptors, which leads to a strong apoptotic signaling, is crucial for inducing apoptosis in cancer cells upon TRAIL treatment. In this review, the current knowledge of oligomerization status of TRAIL receptors is discussed as well as the implications for cancer treatment when using TRAIL-based therapies.
000079636 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-17R$$9info:eu-repo/grantAgreement/ES/ISCIII/PI16-00526$$9info:eu-repo/grantAgreement/ES/MINECO/SAF2016-76338-R
000079636 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000079636 590__ $$a6.126$$b2019
000079636 591__ $$aONCOLOGY$$b37 / 244 = 0.152$$c2019$$dQ1$$eT1
000079636 592__ $$a1.938$$b2019
000079636 593__ $$aOncology$$c2019$$dQ1
000079636 593__ $$aCancer Research$$c2019$$dQ1
000079636 655_4 $$ainfo:eu-repo/semantics/review$$vinfo:eu-repo/semantics/publishedVersion
000079636 700__ $$0(orcid)0000-0002-8486-8514$$aMiguel, Diego de
000079636 700__ $$aGallego-Lleyda, Ana$$uUniversidad de Zaragoza
000079636 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, Alberto$$uUniversidad de Zaragoza
000079636 700__ $$0(orcid)0000-0003-3043-147X$$aMartinez-Lostao, Luis$$uUniversidad de Zaragoza
000079636 7102_ $$11008$$2566$$aUniversidad de Zaragoza$$bDpto. Microb.Med.Pr.,Sal.Públ.$$cÁrea Inmunología
000079636 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000079636 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000079636 773__ $$g11, 4 (2019), Art.444 [20 p.]$$pCancers$$tCancers$$x2072-6694
000079636 8564_ $$s697820$$uhttps://zaguan.unizar.es/record/79636/files/texto_completo.pdf$$yVersión publicada
000079636 8564_ $$s105034$$uhttps://zaguan.unizar.es/record/79636/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000079636 909CO $$ooai:zaguan.unizar.es:79636$$particulos$$pdriver
000079636 951__ $$a2020-07-16-09:02:52
000079636 980__ $$aARTICLE