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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Oncología > Microambiente tumoral > DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista >

Lysine 63 polyubiquitination in immunotherapy and in cancer-promoting inflammation
Authors: Martinez-Forero, I. (Iván)
Rouzaut, A. (Ana)
Palazon, A. (Asís)
Dubrot, J. (Juan)
Melero, I. (Ignacio)
Keywords: Immunotherapy/methods
Issue Date: 2009
Publisher: American Asociation for Cancer Research
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ISSN: 1557-3265
Citation: Martinez-Forero I, Rouzaut A, Palazon A, Dubrot J, Melero I. Lysine 63 polyubiquitination in immunotherapy and in cancer-promoting inflammation. Clin Cancer Res 2009 Nov 15;15(22):6751-6757.
Covalent and reversible post-translational modifications of proteins are a common theme in signaling. Ubiquitin conjugation was originally described to target proteins to proteasomal degradation by ubiquitin polymerization involving lysine (K) 48 residues. Differently linked polymers of polyubiquitin have been found that modify proteins without targeting to proteasomal degradation. Instead this pathway creates docking sites for signaling scaffolds that are key to control the nuclear factor-kappaB (NF-kappaB) pathway. Indeed TRAF-2, TRAF-6, and TRAF-3 are E3 ubiquitin ligases that form K63-linked ubiquitin polymers. Therefore signaling via TNF family receptors, IL1R, IL-18R, T-cell receptor (TCR), and Toll-like receptors (TLR) use this type of post-translational modification. Specific enzymes exist (DUBs) that deactivate this system, degrading K63 polyubiquitin chains. Interestingly, mice deficient in these deubiquitinases develop autoimmunity and inflammation. In carcinogenesis, the K63 polyubiquitin pathway is possibly critical for inflammation-driven tumor promotion. The pathway is also critically involved in costimulation of tumor immunity/immunotherapy as well as in the biology of malignant cells themselves. The elements of this new signaling paradigm offer the opportunity for therapeutic exploitation and drug discovery.
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Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología hepatitis virales - Artículos de revista
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DA - Medicina - Medicina Interna - Artículos de revista
DA - Ciencias - Bioquímica y Biología molecular - Artículos de Revista
DA - CIMA - Oncología - Microambiente tumoral - Artículos de revista

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