@article{74cc7ab8de074dc88200f9ff875682ba,
title = "Immune regulation by protein ubiquitination: roles of the E3 ligases VHL and Itch",
abstract = "Protein ubiquitination is an important means of post-translational modification which plays an essential role in the regulation of various aspects of leukocyte development and function. The specificity of ubiquitin tagging to a protein substrate is determined by E3 ubiquitin ligases via defined E3-substrate interactions. In this review, we will focus on two E3 ligases, VHL and Itch, to discuss the latest progress in understanding their roles in the differentiation and function of CD4+ T helper cell subsets, the stability of regulatory T cells, effector function of CD8+ T cells, as well as the development and maturation of innate lymphoid cells. The biological implications of these E3 ubiquitin ligases will be highlighted in the context of normal and dysregulated immune responses including the control of homeostasis, inflammation, auto-immune responses and anti-tumor immunity. Further elucidation of the ubiquitin system in immune cells will help in the design of new therapeutic interventions for human immunological diseases and cancer.",
keywords = "Cbl-b, E3 ligase, HIF, Itch, VHL, WWP2, autoimmunity, inflammation, ubiquitin",
author = "Daisuke Aki and Qian Li and Hui Li and Liu, {Yun Cai} and Lee, {Jee Ho}",
note = "Funding Information: We thank the contributions of past and current lab members for their efforts in the VHL and Itch projects, and Ms. S. el Baghdady for text editing. This work is supported by funding from MOST YFA0505802, NSFC81630041, NIH RO1AI123398 and R21AI122258. Daisuke Aki, Qian Li, Hui Li, Yun-Cai Liu and Jee Ho Lee declare that they have no conflict of interest. AM, alveolar macrophage; DKO, double knockout; GC, germinal center; HECT, homologous to the E6AP carboxyl terminus; HIF-1α, hypoxia-inducible factor-1α; IFN-γ, interferon-γ; Ig, immunoglobulin; IL, interleukin; ILC, innate lymphoid cell; mTORC1, mammalian target of rapamycin complex 1; NEDD4, neuronal precursor cell expressed developmentally downregulated protein 4; NDFIP1, NEDD4 family interacting protein 1; PHD, prolyl hydroxylase domain; PLC-γ1, phospholipase c-γ1; PLZF, promyelocytic leukemia zinc finger; Rbx1, ring box protein 1; RING, really interesting new gene; SHP-1, Src homology region 2 domain-containing phosphatase-1; RORγt, retinoid acid-related orphan receptor γ t; TCR, T cell receptor; Tfh, follicular helper T cell; TGF-β, transforming growth factor-β; Th, T helper cell type; Treg, regulatory T cell; VHL, von Hippel-Lindau; ZAP-70, zeta-chain associated protein-70. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2019",
month = jun,
day = "1",
doi = "10.1007/s13238-018-0586-8",
language = "English",
volume = "10",
pages = "395--404",
journal = "Protein and Cell",
issn = "1674-800X",
publisher = "Springer-Verlag GmbH and Co. KG",
number = "6",
}
