Immunity by ubiquitylation: a reversible process of modification.
The conjugation of ubiquitin, a 76-amino-acid peptide, to a protein substrate provides a tag that either marks the labelled protein for degradation or modulates its function. The process of protein ubiquitylation--which is catalysed by coordinated enzymatic reactions that are mediated by enzymes known as E1, E2 and E3--has an important role in the modulation of immune responses. Importantly, protein ubiquitylation is a reversible process, and removal of ubiquitin molecules is mediated by de-ubiquitylating enzymes: for example, A20, which has been implicated in the regulation of immune responses. In addition, the conjugation of ubiquitin-like molecules, such as ISG15 (interferon-stimulated protein of 15 kDa), to proteins is also involved in immune regulation. This Review covers recent progress in our understanding of protein ubiquitylation in the immune system.
Liu
Yun-Cai
YC
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA. yuncail@liai.org
Penninger
Josef
J
Karin
Michael
M
D000818:Animals; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007108:Immune Tolerance / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D025801:Ubiquitin / Q000276:immunology* / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000276:immunology*
D025801:Ubiquitin; D043743:Ubiquitin-Protein Ligase Complexes