Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Circadian rhythms are self-sustained oscillators with a period of 24 h that is based on the output of transcriptional and post-translational feedback loops. Phosphorylation is considered one of the most important post-translational modifications affecting rhythmicity from cyanobacteria to mammals. For example, the lack of cyclin-dependent kinase 5 (CDK5) shortened the period length of the circadian oscillator in the Suprachiasmatic Nuclei (SCN) of mice via the destabilization of the PERIOD 2 (PER2) protein. Here, we show that CDK5 kinase activity and its interaction with clock components, including PER2 and CLOCK, varied over time in mouse embryonic fibroblast cells. Furthermore, the deletion of from cells resulted in a prolonged period and shifted the transcription of clock-controlled genes by about 2 to 4 h with a simple delay of chromatin binding of ARNTL (BMAL1) CLOCK. Taken together, our data indicate that CDK5 is critically involved in regulating the circadian clock in vitro at the molecular level.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946863 | PMC |
| http://dx.doi.org/10.3390/clockssleep4010017 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Quantum chemical optimization and residue-specific stabilization of CDK20 inhibitors in hepatocellular carcinoma.
Mol Divers
September 2025
Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, 11942, Al Kharj, Saudi Arabia.
Cyclin-dependent kinase 20 (CDK20), also known as cell cycle-related kinase (CCRK), plays a pivotal role in hepatocellular carcinoma (HCC) progression by regulating β-catenin signaling and promoting uncontrolled proliferation. Despite its emerging significance, selective small-molecule inhibitors of CDK20 remain unexplored. In this study, a known CDK20 inhibitor, ISM042-2-048, was employed as a reference to retrieve structurally similar compounds from the PubChem database using an 85% similarity threshold.
View Article and Find Full Text PDFChromosome 8 Open Reading Frame 76 (C8orf76) Co-Expressed with Cyclin-Dependent Kinase 4 (CDK4) as a Prognostic Indicator of Colorectal Cancer.
Biomed Environ Sci
August 2025
Gastrointestinal Disease Centre, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei, China.
Objective: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC).
Methods: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram.
Unravelling phosphorylation-induced impacts on inhibitor-CDK2 through multiple independent molecular dynamics simulations and deep learning.
SAR QSAR Environ Res
August 2025
Center for Medical Artificial Intelligence, Shandong University of Traditional Chinese Medicine, Qingdao, China.
Phosphorylation plays an important role in the activity of CDK2 and inhibitor binding, but the corresponding molecular mechanism is still insufficiently known. To address this gap, the current study innovatively integrates molecular dynamics (MD) simulations, deep learning (DL) techniques, and free energy landscape (FEL) analysis to systematically explore the action mechanisms of two inhibitors (SCH and CYC) when CDK2 is in a phosphorylated state and bound state of CyclinE. With the help of MD trajectory-based DL, key functional domains such as the loops L3 loop and L7 are successfully identified.
View Article and Find Full Text PDFTranscriptional condensates enrich phosphorylated PRMT2 to stimulate H3R8me2a deposition and hypoxic response in glioblastoma.
Sci China Life Sci
September 2025
State Key Laboratory of Experimental Hematology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Labora
Histone arginine methylation by protein arginine methyltransferases (PRMTs) is crucial for transcriptional regulation and is implicated in cancers. Despite their therapeutic potential, some PRMTs present challenges as drug targets due to their context-dependent activities. Here, we demonstrate that hypoxia triggers the rapid condensation of PRMT2, which is essential for its histone H3R8 asymmetric dimethylation (H3R8me2a) activity.
View Article and Find Full Text PDFMultimode neural population coding of diverse innate fear response by mitral and tufted cells.
Cell Rep
September 2025
International Joint Laboratory for Drug Target of Critical Illnesses, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China; Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. Electronic address:
Neurons that encode odor information are fundamental to innate fear processes, yet how mitral/tufted (M/T) cells encode innate fear remains unknown. Here, we identify three different response patterns of M/T cells in the dorsal olfactory bulb (dOB) during active avoidance elicited by non-dehydrogenated 2,4,5-trimethylthiazole (nTMT) through in vivo calcium imaging and multielectrode recordings in mice, including enhanced responses, suppressed responses, and no response. Remarkably, suppressed response M/T cells encode active avoidance, whereas suppressed and enhanced response M/T cells jointly encode passive freezing.
View Article and Find Full Text PDF