ArticlePloS one2016
USP7 and TDP-43: Pleiotropic Regulation of Cryptochrome Protein Stability Paces the Oscillation of the Mammalian Circadian Clock.
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 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Rhythmic TDP-43 affects RNA splicing of USP13, resulting in alteration of BMAL1 ubiquitination.The Journal of cell biology · 2025Article
- The role of cryptochrome (CRY) in cancer: molecular mechanisms and clock-based therapeutic strategies.Acta biochimica et biophysica Sinica · 2025Review
- The ubiquitin-proteasome system in circadian regulation.Frontiers in neuroscience · 2025Review
- Microglial clock dysfunction during neuroinflammation impairs oligodendrocyte progenitor cell recruitment and disrupts neuroimmune homeostasis.Frontiers in immunology · 2025Article
- Circadian rhythm genes and immune cell infiltration in myasthenia gravis: A comprehensive analysis.PloS one · 2025Article
- Forward genetic approach identifies a phylogenetically conserved serine residue critical for the catalytic activity of UBIQUITIN-SPECIFIC PROTEASE 12 in Arabidopsis.Scientific reports · 2024Article
- TRAF7 determines circadian period through ubiquitination and degradation of DBP.Communications biology · 2024Article
- The Change Rate of theBiology · 2024Article
- Phosphorylation of DNA-binding domains of CLOCK-BMAL1 complex for PER-dependent inhibition in circadian clock of mammalian cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TDP-43 deficiency in suprachiasmatic nucleus perturbs rhythmicity of neuroactivity in prefrontal cortex.iScience · 2024Article
- Cryptochrome 2 acetylation attenuates its antiproliferative effect in breast cancer.Cell death & disease · 2023Article
- Circadian gene expression in mouse renal proximal tubule.American journal of physiology. Renal physiology · 2023Article
- UBP12 and UBP13 deubiquitinases destabilize the CRY2 blue light receptor to regulate Arabidopsis growth.Current biology : CB · 2022Article
- MicroRNA: A Key Player for the Interplay of Circadian Rhythm Abnormalities, Sleep Disorders and Neurodegenerative Diseases.Clocks & sleep · 2020Review
- A MAGEL2-deubiquitinase complex modulates the ubiquitination of circadian rhythm protein CRY1.PloS one · 2020Article
- GIGANTEA recruits the UBP12 and UBP13 deubiquitylases to regulate accumulation of the ZTL photoreceptor complex.Nature communications · 2019Article
- Identification of intracellular cavin target proteins reveals cavin-PP1alpha interactions regulate apoptosis.Nature communications · 2019Article
- Ubiquitin-conjugating enzyme UBE2O regulates cellular clock function by promoting the degradation of the transcription factor BMAL1.The Journal of biological chemistry · 2018Article
- FAD Regulates CRYPTOCHROME Protein Stability and Circadian Clock in Mice.Cell reports · 2017Article
- The intricate dance of post-translational modifications in the rhythm of life.Nature structural & molecular biology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian Cryptochromes, CRY1 and CRY2, function as principal regulators of a transcription-translation-based negative feedback loop underlying the mammalian circadian clockwork. An F-box protein, FBXL3, promotes ubiquitination and degradation of CRYs, while FBXL21, the closest paralog of FBXL3, ubiquitinates CRYs but leads to stabilization of CRYs. Fbxl3 knockout extremely lengthened the circadian period, and deletion of Fbxl21 gene in Fbxl3-deficient mice partially rescued the period-lengthening phenotype, suggesting a key role of CRY protein stability for maintenance of the circadian periodicity. Here, we employed a proteomics strategy to explore regulators for the protein stability of CRYs. We found that ubiquitin-specific protease 7 (USP7 also known as HAUSP) associates with CRY1 and CRY2 and stabilizes CRYs through deubiquitination. Treatment with USP7-specific inhibitor or Usp7 knockdown shortened the circadian period of the cellular rhythm. We identified another CRYs-interacting protein, TAR DNA binding protein 43 (TDP-43), an RNA-binding protein. TDP-43 stabilized CRY1 and CRY2, and its knockdown also shortened the circadian period in cultured cells. The present study identified USP7 and TDP-43 as the regulators of CRY1 and CRY2, underscoring the significance of the stability control process of CRY proteins for period determination in the mammalian circadian clockwork.
Indexed as
Identifiers
What OpenQuestion holds
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.