Circadian Clock Control by SUMOylation of BMAL1

@article{Cardone2005CircadianCC,
  title={Circadian Clock Control by SUMOylation of BMAL1},
  author={Luca Cardone and Jun Hirayama and Francesca Giordano and Teruya Tamaru and Jorma J. Palvimo and Paolo Sassone-Corsi},
  journal={Science},
  year={2005},
  volume={309},
  pages={1390 - 1394}
}
The molecular machinery that governs circadian rhythmicity is based on clock proteins organized in regulatory feedback loops. Although posttranslational modification of clock proteins is likely to finely control their circadian functions, only limited information is available to date. Here, we show that BMAL1, an essential transcription factor component of the clock mechanism, is SUMOylated on a highly conserved lysine residue (Lys259) in vivo. BMAL1 shows a circadian pattern of SUMOylation… 
View on AAAS
bio.gnu.ac.kr
312 Citations
Highly Influential Citations
16
Background Citations
134
Methods Citations
6
Results Citations
1

312 Citations

Citation Type

Citation Type

CLOCK-mediated acetylation of BMAL1 controls circadian function
TLDR
It is shown that CLOCK also acetylates a non-histone substrate: its own partner, BMAL1, is specifically acetylated on a unique, highly conserved Lys 537 residue, revealing the enzymatic interplay between two clock core components is crucial for the circadian machinery.
Posttranslational and epigenetic regulation of the CLOCK/BMAL1 complex in the mammalian
TLDR
How the CLOCK and BMAL1 activities are regulated by intracellular distribution, posttranslational modification, and the recruitment of various epigenetic regulators in response to circadian and cellular signaling pathways is reviewed.
Sumoylation Contributes to Timekeeping and Temperature Compensation of the Plant Circadian Clock
TLDR
Sumoylation is established, the posttranslational modification of target proteins by the covalent attachment of the small ubiquitin-like modifier protein SUMO, as a novel mechanism regulating key clock properties in the model plant Arabidopsis, and it is observed that the period defects in sumoylation mutant plants are strongly differential across temperature.
Circadian Regulator CLOCK Is a Histone Acetyltransferase
CLOCK leaves its mark on histones.
Dual Modification of BMAL1 by SUMO2/3 and Ubiquitin Promotes Circadian Activation of the CLOCK/BMAL1 Complex
TLDR
It is shown that modification by SUMO localizes BMAL1 exclusively to the promyelocytic leukemia nuclear body (NB) and simultaneously promotes its transactivation and ubiquitin-dependent degradation.
Chromatin remodeling and circadian control: master regulator CLOCK is an enzyme.
TLDR
The findings reveal that the enzymatic interplay between two clock core components is crucial for the circadian machinery.
Phosphorylation of LSD1 by PKCα is crucial for circadian rhythmicity and phase resetting.
A central role for ubiquitination within a circadian clock protein modification code
TLDR
It is proposed that ubiquitination is a key element in a clock protein modification code that orchestrates clock mechanisms and circadian behavior over the daily cycle.
The BMAL1 C terminus regulates the circadian transcription feedback loop.
TLDR
A molecular genetic screening assay for mutant circadian clock proteins that is based on real-time circadian rhythm monitoring in cultured fibroblasts suggests that the C-terminal region of BMAL1 is involved in determining the balance between circadian transcriptional activation and suppression.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 31 REFERENCES
Posttranslational Mechanisms Regulate the Mammalian Circadian Clock
BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system.
TLDR
Results provide evidence for an additional level of circadian system control, which is based on regulation of transcriptional activity or/and availability of CLOCK/BMAL1 complex, and all posttranslational events described in this study are coupled with active transactivation complex formation, which argues for their significant functional role.
Genetics of the mammalian circadian system: Photic entrainment, circadian pacemaker mechanisms, and posttranslational regulation.
TLDR
Three aspects of the mammalian circadian story in mammals are focused on: the genetics of the photic entrainment pathway; the molecular components of the circadian pacemaker in the hypothalamic suprachiasmatic nucleus; and the role of posttranslational regulation of circadian elements.
Mop3 Is an Essential Component of the Master Circadian Pacemaker in Mammals
Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim.
TLDR
The Drosophila CLOCK protein was shown to induce transcription of the circadian rhythm genes period and timeless, and PERIOD and TIMELESS proteins blocked dCLOCK's ability to transactivate their promoters via the E-box.
Light-independent role of CRY1 and CRY2 in the mammalian circadian clock.
TLDR
Mammalian CRY1 and CRY2 are shown to act as light-independent inhibitors of CLOCK-BMAL1, the activator driving Per1 transcription and probably regulate Per 1 transcriptional cycling by contacting both the Activator and its feedback inhibitors.
Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms
TLDR
It is shown that mice lacking the Cry1 or Cry2 protein display accelerated and delayed free-running periodicity of locomotor activity, respectively, which suggests that, in addition to a possible photoreceptor and antagonistic clock-adjusting function, both proteins are essential for the maintenance of circadian rhythmicity.
Clock Genes in Cell Clocks: Roles, Actions, and Mysteries
  • H. Okamura
  • Biology
    Journal of biological rhythms
  • 2004
TLDR
The prominence of circadian organization may not apply equally to all tissues under all conditions, as some tissues, such as testis, express clock genes whose function, if any, remains unclear.
Nucleocytoplasmic shuttling and phosphorylation of BMAL1 are regulated by circadian clock in cultured fibroblasts
TLDR
This work has shown that clock proteins are an important part of the mammalian circadian clock mechanism and the molecular clockwork that cause these fundamental feedback loops to stably oscillate with a ∼24 h‐periodicity remain unclear.
Altered behavioral rhythms and clock gene expression in mice with a targeted mutation in the Period1 gene
TLDR
The generation of mice in which the founding member of the Per family, Per1, has been inactivated by homologous recombination is presented, demonstrating that Per1 plays a distinct role within the Perfamily, as it may be involved predominantly in peripheral clocks and/or in the output pathways of the circadian clock.
...
1
2
3
4
...