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  • The E3 ubiquitin ligase Peli1 regulates the metabolic actions of mTORC1 to suppress antitumor T cell responses.

The E3 ubiquitin ligase Peli1 regulates the metabolic actions of mTORC1 to suppress antitumor T cell responses.

The EMBO journal (2020-11-21)
Chun-Jung Ko, Lingyun Zhang, Zuliang Jie, Lele Zhu, Xiaofei Zhou, Xiaoping Xie, Tianxiao Gao, Jin-Young Yang, Xuhong Cheng, Shao-Cong Sun
ABSTRACT

Metabolic fitness of T cells is crucial for immune responses against infections and tumorigenesis. Both the T cell receptor (TCR) signal and environmental cues contribute to the induction of T cell metabolic reprogramming, but the underlying mechanism is incompletely understood. Here, we identified the E3 ubiquitin ligase Peli1 as an important regulator of T cell metabolism and antitumor immunity. Peli1 ablation profoundly promotes tumor rejection, associated with increased tumor-infiltrating CD4 and CD8 T cells. The Peli1-deficient T cells display markedly stronger metabolic activities, particularly glycolysis, than wild-type T cells. Peli1 controls the activation of a metabolic kinase, mTORC1, stimulated by both the TCR signal and growth factors, and this function of Peli1 is mediated through regulation of the mTORC1-inhibitory proteins, TSC1 and TSC2. Peli1 mediates non-degradative ubiquitination of TSC1, thereby promoting TSC1-TSC2 dimerization and TSC2 stabilization. These results establish Peli1 as a novel regulator of mTORC1 and downstream mTORC1-mediated actions on T cell metabolism and antitumor immunity.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
インスリン 溶液 ヒト, sterile-filtered, BioXtra, suitable for cell culture
Sigma-Aldrich
モノクロナール抗β-アクチン マウス宿主抗体, clone AC-74, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
抗LC3B ウサギ宿主抗体, ~1 mg/mL, affinity isolated antibody, buffered aqueous solution