ArticlePloS one2016
USP2-45 Is a Circadian Clock Output Effector Regulating Calcium Absorption at the Post-Translational Level.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- Calorie restriction modulates the transcription of genes related to stress response and longevity in human muscle: The CALERIE study.Aging cell · 2023Trial
- Timekeepers of the gut: host circadian rhythms and microbial modulators.Life metabolism · 2026Review
- Ubiquitin-Specific Protease 2 (USP2) as a Modulator of Energy Metabolism: A Review of Studies Using Animal and Cellular Models.Biomedicines · 2026Review
- USP2 promotes metabolic dysfunction-associated steatotic liver disease progression via stabilization of PPARγ.Cell death and differentiation · 2026Article
- Transcriptional regulation of ubiquitin specific peptidase 2b by farnesoid X receptor and its implications in the pathogenesis of hepatocellular carcinoma.American journal of cancer research · 2026Article
- DCAF7 recruits USP2 to facilitate hepatocellular carcinoma progression by suppressing clockophagy-induced ferroptosis.Cell death & disease · 2025Article
- Identification of USP2 as a novel target to induce degradation of KRAS in myeloma cells.Acta pharmaceutica Sinica. B · 2024Article
- Targeting the deubiquitinaseOncology reports · 2023Review
- Effect of circadian clock and claudin regulations on inulin-induced calcium absorption in the mouse intestinal tract.Bioscience of microbiota, food and health · 2023Article
- Sex Differences in Molecular Rhythms in the Human Cortex.Biological psychiatry · 2022Article
- Article
- USP2-Related Cellular Signaling and Consequent Pathophysiological Outcomes.International journal of molecular sciences · 2021Review
- Article
- Downregulation of ubiquitin-specific protease 2 possesses prognostic and diagnostic value and promotes the clear cell renal cell carcinoma progression.Annals of translational medicine · 2020Article
- Calcium Sets the Clock in Ameloblasts.Frontiers in physiology · 2020Article
- The serine-threonine kinase PIM3 is an aldosterone-regulated protein in the distal nephron.Physiological reports · 2019Article
- Circadian Clock Genes in Diabetic Kidney Disease (DKD).Current diabetes reports · 2019Review
- Circadian rhythms and the kidney.Nature reviews. Nephrology · 2018Review
- The Molecular Mechanisms of Regulation on USP2's Alternative Splicing and the Significance of Its Products.International journal of biological sciences · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian circadian clock influences most aspects of physiology and behavior through the transcriptional control of a wide variety of genes, mostly in a tissue-specific manner. About 20 clock-controlled genes (CCGs) oscillate in virtually all mammalian tissues and are generally considered as core clock components. One of them is Ubiquitin-Specific Protease 2 (Usp2), whose status remains controversial, as it may be a cogwheel regulating the stability or activity of core cogwheels or an output effector. We report here that Usp2 is a clock output effector related to bodily Ca2+ homeostasis, a feature that is conserved across evolution. Drosophila with a whole-body knockdown of the orthologue of Usp2, CG14619 (dUsp2-kd), predominantly die during pupation but are rescued by dietary Ca2+ supplementation. Usp2-KO mice show hyperabsorption of dietary Ca2+ in small intestine, likely due to strong overexpression of the membrane scaffold protein NHERF4, a regulator of the Ca2+ channel TRPV6 mediating dietary Ca2+ uptake. In this tissue, USP2-45 is found in membrane fractions and negatively regulates NHERF4 protein abundance in a rhythmic manner at the protein level. In clock mutant animals (Cry1/Cry2-dKO), rhythmic USP2-45 expression is lost, as well as the one of NHERF4, confirming the inverse relationship between USP2-45 and NHERF4 protein levels. Finally, USP2-45 interacts in vitro with NHERF4 and endogenous Clathrin Heavy Chain. Taken together these data prompt us to define USP2-45 as the first clock output effector acting at the post-translational level at cell membranes and possibly regulating membrane permeability of Ca2+.
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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.