ArticleMolecular endocrinology (Baltimore, Md.)2014
USP7 attenuates hepatic gluconeogenesis through modulation of FoxO1 gene promoter occupancy.
Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 42 citations in OpenAlex.
- USP7 inhibits FOXO1 activity in chronic lymphocytic leukaemia cells enhancing cell survival.Molecular oncology · 2026Article
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Ubiquitination modifications as central regulators of metabolic dysfunction in type 2 diabetes mellitus.Frontiers in endocrinology · 2026Review
- USP7 at the Crossroads of Ubiquitin Signaling, Cell Cycle, and Tumorigenesis.Molecules (Basel, Switzerland) · 2025Review
- The ubiquitin-proteasome system: A potential target for the MASLD.Acta pharmaceutica Sinica. B · 2025Review
- CAMKIIδ Reinforces Lipid Metabolism and Promotes the Development of B Cell Lymphoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ubiquitination and Metabolic Disease.Advances in experimental medicine and biology · 2024Review
- Forkhead box O1 in metabolic dysfunction-associated fatty liver disease: molecular mechanisms and drug research.Frontiers in nutrition · 2024Review
- Deubiquitinases in cancer.Nature reviews. Cancer · 2023Review
- Ubiquitin-Specific Proteases (USPs) and Metabolic Disorders.International journal of molecular sciences · 2023Review
- Characterizing (un)binding mechanism of USP7 inhibitors to unravel the cause of enhanced binding potencies at allosteric checkpoint.Protein science : a publication of the Protein Society · 2022Article
- The transcriptional corepressor CtBP2 serves as a metabolite sensor orchestrating hepatic glucose and lipid homeostasis.Nature communications · 2021Article
- The role of USP7 in the Shoc2-ERK1/2 signaling axis and Noonan-like syndrome with loose anagen hair.Journal of cell science · 2021Article
- Regulation of Cancer Metabolism by Deubiquitinating Enzymes: The Warburg Effect.International journal of molecular sciences · 2021Review
- Ubiquitin-related processes and innate immunity in C. elegans.Cellular and molecular life sciences : CMLS · 2021Review
- Forkhead Box Protein O1: Functional Diversity and Post-Translational Modification, a New Therapeutic Target?Drug design, development and therapy · 2021Review
- RNA-seq analysis provides insight into molecular adaptations of Andrias davidianus.Development genes and evolution · 2019Article
- Article
- Repression of Transcriptional Activity of Forkhead Box O1 by Histone Deacetylase Inhibitors Ameliorates Hyperglycemia in Type 2 Diabetic Rats.International journal of molecular sciences · 2018Article
- Discovery and characterization of highly potent and selective allosteric USP7 inhibitors.Nature chemical biology · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatic forkhead protein FoxO1 is a key component of systemic glucose homeostasis via its ability to regulate the transcription of rate-limiting enzymes in gluconeogenesis. Important in the regulation of FoxO1 transcriptional activity are the modifying/demodifying enzymes that lead to posttranslational modification. Here, we demonstrate the functional interaction and regulation of FoxO1 by herpesvirus-associated ubiquitin-specific protease 7 (USP7; also known as herpesvirus-associated ubiquitin-specific protease, HAUSP), a deubiquitinating enzyme. We show that USP7-mediated mono-deubiquitination of FoxO1 results in suppression of FoxO1 transcriptional activity through decreased FoxO1 occupancy on the promoters of gluconeogenic genes. Knockdown of USP7 in primary hepatocytes leads to increased expression of FoxO1-target gluconeogenic genes and elevated glucose production. Consistent with this, USP7 gain-of-function suppresses the fasting/cAMP-induced activation of gluconeogenic genes in hepatocyte cells and in mouse liver, resulting in decreased hepatic glucose production. Notably, we show that the effects of USP7 on hepatic glucose metabolism depend on FoxO1. Together, these results place FoxO1 under the intimate regulation of deubiquitination and glucose metabolic control with important implication in diseases such as diabetes.
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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.