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E3 Ubiquitin Ligase Casitas B Lineage Lymphoma-B and Its Potential Therapeutic Implications for Immunotherapy Publisher Pubmed



Jafari D1, 2 ; Mousavi MJ3, 4 ; Keshavarz Shahbaz S5 ; Jafarzadeh L4 ; Tahmasebi S6 ; Spoor J7 ; Esmaeilzadeh A1, 2, 8
Authors
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Authors Affiliations
  1. 1. Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
  2. 2. Immunotherapy Research and Technology Group, Zanjan University of Medical Sciences, Zanjan, Iran
  3. 3. Department of Hematology, Faculty of Allied medicine, Bushehr University of Medical Sciences, Bushehr, Iran
  4. 4. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  6. 6. Department of Immunology, School of public health, Tehran University of Medical Sciences, Tehran, Iran
  7. 7. Erasmus University Medical Centre, Erasmus University Rotterdam, Rotterdam, Netherlands
  8. 8. Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran

Source: Clinical and Experimental Immunology Published:2021


Abstract

The distinction of self from non-self is crucial to prevent autoreactivity and ensure protection from infectious agents and tumors. Maintaining the balance between immunity and tolerance of immune cells is strongly controlled by several sophisticated regulatory mechanisms of the immune system. Among these, the E3 ligase ubiquitin Casitas B cell lymphoma-b (Cbl-b) is a newly identified component in the ubiquitin-dependent protein degradation system, which is thought to be an important negative regulator of immune cells. An update on the current knowledge and new concepts of the relevant immune homeostasis program co-ordinated by Cbl-b in different cell populations could pave the way for future immunomodulatory therapies of various diseases, such as autoimmune and allergic diseases, infections, cancers and other immunopathological conditions. In the present review, the latest findings are comprehensively summarized on the molecular structural basis of Cbl-b and the suppressive signaling mechanisms of Cbl-b in physiological and pathological immune responses, as well as its emerging potential therapeutic implications for immunotherapy in animal models and human diseases. © 2020 British Society for Immunology