E3 ubiquitin ligase Cbl-b in innate and adaptive immunity

Cell Cycle. 2014;13(12):1875-84. doi: 10.4161/cc.29213. Epub 2014 May 14.

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.

Keywords: Cbl-b; biological function; immune disease and therapy; molecular struction; signaling mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity / physiology*
  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / therapy
  • Humans
  • Immunity, Innate / physiology*
  • Immunotherapy
  • Inflammation / immunology
  • Inflammation / therapy
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Organ Specificity
  • Protein Conformation
  • Proto-Oncogene Proteins c-cbl / chemistry
  • Proto-Oncogene Proteins c-cbl / genetics
  • Proto-Oncogene Proteins c-cbl / metabolism*
  • Signal Transduction / physiology
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • CBLB protein, human
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases