79636 20200716101446.0 doi 10.3390/cancers11040444 sideral 112239 ART-2019-112239 eng (orcid)0000-0003-2156-8378 Naval, Javier Universidad de Zaragoza Importance of TRAIL molecular anatomy in receptor oligomerization and signaling. Implications for cancer therapy 2019 Access copy available to the general public Unrestricted (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. info:eu-repo/grantAgreement/ES/DGA/B31-17R info:eu-repo/grantAgreement/ES/ISCIII/PI16-00526 info:eu-repo/grantAgreement/ES/MINECO/SAF2016-76338-R info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 6.126 2019 ONCOLOGY 37 / 244 = 0.152 2019 Q1 T1 1.938 2019 Oncology 2019 Q1 Cancer Research 2019 Q1 info:eu-repo/semantics/review info:eu-repo/semantics/publishedVersion (orcid)0000-0002-8486-8514 Miguel, Diego de Gallego-Lleyda, Ana Universidad de Zaragoza (orcid)0000-0002-5175-8394 Anel, Alberto Universidad de Zaragoza (orcid)0000-0003-3043-147X Martinez-Lostao, Luis Universidad de Zaragoza 1008 566 Universidad de Zaragoza Dpto. Microb.Med.Pr.,Sal.Públ. Área Inmunología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 11, 4 (2019), Art.444 [20 p.] Cancers Cancers 2072-6694 697820 http://zaguan.unizar.es/record/79636/files/texto_completo.pdf Versión publicada 105034 http://zaguan.unizar.es/record/79636/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:79636 articulos driver 2020-07-16-09:02:52 ARTICLE