title: E3 ubiquitin ligase Cbl-b in innate and adaptive immunity.
abstract: Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b), a RING finger E3 ubiquitin-protein ligase, has been demonstrated to play a crucial role in establishing the threshold for T-cell activation and controlling peripheral T-cell tolerance via multiple mechanisms. Accumulating evidence suggests that Cbl-b also regulates innate immune responses and plays an important role in host defense to pathogens. Understanding the signaling pathways regulated by Cbl-b in innate and adaptive immune cells is therefore essential for efficient manipulation of Cbl-b in emerging immunotherapies for human disorders such as autoimmune diseases, allergic inflammation, infections, and cancer. In this article, we review the latest developments in the molecular structural basis of Cbl-b function, the regulation of Cbl-b expression, the signaling mechanisms of Cbl-b in immune cells, as well as the biological function of Cbl-b in physiological and pathological immune responses in animal models and human diseases.
authors.affiliation: Laboratory of Immunohematology; Beijing Institute of Transfusion Medicine; Beijing, PR China; Department of Microbial Infection and Immunity; The Ohio State University; Columbus, OH USA.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Laboratory of Immunohematology; Beijing Institute of Transfusion Medicine; Beijing, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: School of Pathology and Laboratory Medicine; University of Western Australia; Crawley, Western Australia, Australia.
authors.forename: Wallace Y
authors.initials: WY
authors.lastname: Langdon
authors.affiliation: Department of Microbial Infection and Immunity; The Ohio State University; Columbus, OH USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D056704:Adaptive Immunity / Q000502:physiology*; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007167:Immunotherapy; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D009928:Organ Specificity; D011487:Protein Conformation; D000090063:Proto-Oncogene Mas; D050721:Proto-Oncogene Proteins c-cbl / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C492211:CBLB protein, human; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases
keywords: Cbl-b; biological function; immune disease and therapy; molecular struction; signaling mechanism