ArticleThe Journal of experimental medicine2020
Mevalonate metabolism-dependent protein geranylgeranylation regulates thymocyte egress.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Uncovering protein prenylation in Th1 cells: novel prenylation sites and insights into statin and farnesyltransferase inhibition.BMC biology · 2025Article
- Intrathymic Cell Migration: Implications in Thymocyte Development and T Lymphocyte Repertoire Formation.Advances in experimental medicine and biology · 2025Review
- Article
- Protein lipidation in health and disease: molecular basis, physiological function and pathological implication.Signal transduction and targeted therapy · 2024Review
- Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizingActa pharmaceutica Sinica. B · 2023Article
- Metabolic signature and proteasome activity controls synovial migration ofFrontiers in immunology · 2023Article
- Infection by a helminth parasite is associated with changes in DNA methylation in the house sparrow.Ecology and evolution · 2022Article
- Metabolic regulation of T cell development.Frontiers in immunology · 2022Review
- Thymus and autoimmunity.Seminars in immunopathology · 2021Review
- Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications.Journal of inflammation research · 2021Review
- A Requirement of Protein Geranylgeranylation for Chemokine Receptor Signaling and Th17 Cell Function in an Animal Model of Multiple Sclerosis.Frontiers in immunology · 2021Article
- Protein Prenylation Drives Discrete Signaling Programs for the Differentiation and Maintenance of Effector TCell metabolism · 2020Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Thymocyte egress is a critical determinant of T cell homeostasis and adaptive immunity. Despite the roles of G protein-coupled receptors in thymocyte emigration, the downstream signaling mechanism remains poorly defined. Here, we report the discrete roles for the two branches of mevalonate metabolism-fueled protein prenylation pathway in thymocyte egress and immune homeostasis. The protein geranylgeranyltransferase Pggt1b is up-regulated in single-positive thymocytes, and loss of Pggt1b leads to marked defects in thymocyte egress and T cell lymphopenia in peripheral lymphoid organs in vivo. Mechanistically, Pggt1b bridges sphingosine-1-phosphate and chemokine-induced migratory signals with the activation of Cdc42 and Pak signaling and mevalonate-dependent thymocyte trafficking. In contrast, the farnesyltransferase Fntb, which mediates a biochemically similar process of protein farnesylation, is dispensable for thymocyte egress but contributes to peripheral T cell homeostasis. Collectively, our studies establish context-dependent effects of protein prenylation and unique roles of geranylgeranylation in thymic egress and highlight that the interplay between cellular metabolism and posttranslational modification underlies immune homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.