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

The EMBO Journal
Chun-Jung KoShao-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.

References

Mar 29, 1995·International Journal of Cancer. Journal International Du Cancer·L AagaardJ Bartek
Dec 18, 2001·Journal of Mass Spectrometry : JMS·J Peng, S P Gygi
Aug 13, 2002·Nature Cell Biology·Ken InokiKun-Liang Guan
Mar 30, 2004·Genesis : the Journal of Genetics and Development·Giuseppe TestaA Francis Stewart
Feb 9, 2006·The Journal of Biological Chemistry·Huira Chong-KoperaKun-Liang Guan
Nov 17, 2007·Genes & Development·Noboru Mizushima
May 10, 2008·The Biochemical Journal·Jingxiang Huang, Brendan D Manning
Jan 10, 2009·Annual Review of Immunology·Jennifer E Smith-GarvinMartha S Jordan
Aug 2, 2011·European Journal of Immunology·Thomas F O'BrienXiao-Ping Zhong
Oct 12, 2011·Annual Review of Cell and Developmental Biology·Sophia Y Lunt, Matthew G Vander Heiden
Apr 21, 2012·Nature Reviews. Immunology·Hongbo Chi
May 5, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Adam T Waickman, Jonathan D Powell
Jan 10, 2013·Annual Review of Immunology·Nancie J MacIverJeffrey C Rathmell
Feb 1, 2013·Nature·Sanae Shoji-KawataBeth Levine
Feb 5, 2013·Seminars in Immunology·Kai Yang, Hongbo Chi
Oct 12, 2013·Science·Erika L PearceRussell G Jones
Nov 1, 1994·Journal of the American Society for Mass Spectrometry·J K EngJ R Yates
Jan 22, 2014·Nature Reviews. Immunology·Paul N Moynagh
Jun 26, 2014·Nature Reviews. Immunology·Kristen N Pollizzi, Jonathan D Powell
Feb 6, 2015·The Journal of Clinical Investigation·Young Chul Kim, Kun-Liang Guan
Mar 13, 2015·Transcription·Hu Zeng, Hongbo Chi
Nov 9, 2016·Seminars in Immunology·Luís AlmeidaTim Sparwasser
Apr 2, 2017·Cytokine & Growth Factor Reviews·J N Rashida GnanaprakasamRuoning Wang
May 6, 2017·Cell·Michael D BuckErika L Pearce
Feb 2, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Dayana B Rivadeneira, Greg M Delgoffe
Feb 7, 2018·Frontiers in Immunology·Aurélie DurgeauFathia Mami-Chouaib
Nov 16, 2018·Nature·Laura Poillet-PerezEileen White
Mar 28, 2019·Nature Reviews. Clinical Oncology·Xiaoyun LiPing-Chih Ho
Apr 11, 2019·Cell Reports·Lindsay DeVorkinJulian J Lum

❮ Previous
Next ❯

Citations

Oct 1, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ewa OleszyckaPaul N Moynagh

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.