The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity

Title
The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity
Author(s)
장재훈Mikyoung Chang[Mikyoung Chang]Wei Jin[Wei Jin]Yichuan Xiao[Yichuan Xiao]George C Brittain[George C Brittain]Jiayi Yu[Jiayi Yu]Xiaofei Zhou[Xiaofei Zhou]Yi-Hong Wang[Yi-Hong Wang]Pingwei Li[Pingwei Li]Brian A Rabinovich[Brian A Rabinovich]Patrick Hwu[Patrick Hwu]Xuhong Cheng[Xuhong Cheng]Shao-Cong Sun[Shao-Cong Sun]
Keywords
DEUBIQUITINATING ENZYME CYLD; KAPPA-B ACTIVATION; C-REL; PELLINO PROTEINS; LYMPHOCYTE-PROLIFERATION; TRANSCRIPTION FACTORS; IL-2 PROMOTER; TGF-BETA; INTERLEUKIN-2; MECHANISMS
Issue Date
201110
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE IMMUNOLOGY, v.12, no.10, pp.1002 - U112
Abstract
T cell activation is subject to tight regulation to avoid inappropriate responses to self antigens. Here we show that genetic deficiency in the ubiquitin ligase Peli1 caused hyperactivation of T cells and rendered T cells refractory to suppression by regulatory T cells and transforming growth factor-beta (TGF-beta). As a result, Peli1-deficient mice spontaneously developed autoimmunity characterized by multiorgan inflammation and autoantibody production. Peli1 deficiency resulted in the nuclear accumulation of c-Rel, a member of the NF-kappa B family of transcription factors with pivotal roles in T cell activation. Peli1 negatively regulated c-Rel by mediating its Lys48 (K48) ubiquitination. Our results identify Peli1 as a critical factor in the maintenance of peripheral T cell tolerance and demonstrate a previously unknown mechanism of c-Rel regulation.
URI
http://hdl.handle.net/YU.REPOSITORY/24390http://dx.doi.org/10.1038/ni.2090
ISSN
1529-2908
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약학대학 > 약학부 > Articles
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