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Circadian regulation of c-MYC in mice

Zhenxing Liu1, Christopher P Selby1, Yanyan Yang1

  • 1Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7260.

Proceedings of the National Academy of Sciences of the United States of America
|August 21, 2020
PubMed

Insights

Disrupting the circadian clock affects the oncogene MYC. Mutations in CRY1/CRY2 decrease MYC, while BMAL1 mutations increase MYC protein levels in mouse spleen.

Area of Science:

  • Molecular Biology
  • Chronobiology
  • Oncology

Background:

  • The circadian clock regulates a significant portion of mammalian gene expression, including key cancer-related genes like MYC.
  • The interplay between circadian clock genes and the oncogene MYC is complex, influencing both transcription and protein stability.

Purpose of the Study:

  • To investigate the impact of essential circadian clock gene mutations (Bmal1, Cry1, Cry2) on MYC expression and tumorigenesis.
  • To elucidate the role of specific clock gene arms (positive and negative transcriptional-translational feedback loops) in regulating MYC levels.

Main Methods:

  • Utilized mouse models with targeted mutations in the core clock genes Bmal1, Cry1, and Cry2.
  • Analyzed c-MYC expression and protein levels in the spleen of these mutant mice.

Main Results:

  • Mutation of both Cry1 and Cry2 (disrupting the negative feedback loop) led to down-regulation of c-MYC.
  • Mutation of Bmal1 (disrupting the positive feedback loop) resulted in up-regulation of c-MYC protein in the spleen.

Conclusions:

  • Circadian clock disruption significantly impacts MYC oncogene expression.
  • These findings are crucial for understanding the connection between circadian clock disruption and cancer development, informing future therapeutic models.
Keywords:
BMAL1c-MYCcircadian clockcryptochromestranscription regulation

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