ArticleMolecular and cellular biology2006
BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1 heterodimer.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 161 citations in OpenAlex.
- Marine n-3 polyunsaturated fatty acids slow sleep impairment progression by regulating central circadian rhythms in type 2 diabetes.Cell reports. Medicine · 2025Trial
- BMAL1 in cardiovascular diseases: Molecular mechanisms, circadian regulation and translational perspectives (Review).Molecular medicine reports · 2026Review
- BMAL1 Dysregulation as a Contributing Mechanism Linking Obesity to Oocyte and Endometrial Dysfunction in IVF.International journal of molecular sciences · 2026Review
- Rhythmic nuclear import mediated by importins regulates the Neurospora circadian clock.Genetics · 2026Article
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Rhythmic Nuclear Import Mediated by Importins Regulates thebioRxiv : the preprint server for biology · 2026Article
- Immediate nuclear accumulation of BMAL1 to regulate cellular circadian clock synchronization.Communications biology · 2025Article
- Article
- Circadian Regulation of Neuronal Membrane Capacitance-Mechanisms and Implications for Neural Computation and Behavior.International journal of molecular sciences · 2025Review
- O-GlcNAcylation of nuclear proteins in the mouse liver exhibit daily oscillations that are influenced by meal timing.PLoS biology · 2025Article
- Mealtime alters daily rhythm in nuclear O-GlcNAc proteome to regulate hepatic gene expression.bioRxiv : the preprint server for biology · 2025Article
- CHRONO regulates the circadian clock via the REV-ERBα - BMAL1 loop.Npj biological timing and sleep · 2025Article
- Long non-coding RNA AK023617 orchestrates atherosclerosis by regulating the circadian rhythm of immunity-related GTPase family M protein in macrophages.Non-coding RNA research · 2025Article
- Proteomic insights into circadian transcription regulation: novel E-box interactors revealed by proximity labeling.Genes & development · 2024Article
- The Function, Regulation, and Mechanism of Protein Turnover in Circadian Systems inInternational journal of molecular sciences · 2024Review
- Synaptic BMAL1 phosphorylation controls circadian hippocampal plasticity.Science advances · 2023Article
- Circadian clock regulator Bmal1 gates axon regeneration via Tet3 epigenetics in mouse sensory neurons.Nature communications · 2023Article
- Control of circadian rhythm on cortical excitability and synaptic plasticity.Frontiers in neural circuits · 2023Review
- Rhythmic transcription of Bmal1 stabilizes the circadian timekeeping system in mammals.Nature communications · 2022Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CLOCK and BMAL1 are bHLH-PAS-containing transcription factors that bind to E-box elements and are indispensable for expression of core circadian clock components such as the Per and Cry genes. A key step in expression is the heterodimerization of CLOCK and BMAL1 and their accumulation in the nucleus with an approximately 24-h periodicity. We show here that nucleocytoplasmic shuttling of BMAL1 is essential for transactivation and for degradation of the CLOCK/BMAL1 heterodimer. Using serial deletions and point mutants, we identified a functional nuclear localization signal and Crm1-dependent nuclear export signals in BMAL1. Transient-transfection experiments revealed that heterodimerization of CLOCK and BMAL1 accelerates their turnover, as well as E-box-dependent clock gene transcription. Moreover, in embryonic mouse fibroblasts, robust transcription of Per2 is tightly associated with massive degradation of the CLOCK/BMAL1 heterodimer. CRY proteins suppressed this process during the transcription-negative phase and led to nuclear accumulation of the CLOCK/BMAL1 heterodimer. Thus, these findings suggest that the decrease of BMAL1 abundance during the circadian cycle reflects robust transcriptional activation of clock genes rather than inhibition of BMAL1 synthesis.
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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.