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Metastasis-associated protein 1 is an integral component of the circadian molecular machinery

Da-Qiang Li1, Suresh B Pakala, Sirigiri Divijendra Natha Reddy

  • 11] Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, District of Columbia 20037, USA [2].

Nature Communications
|October 4, 2013
PubMed

Insights

Metastasis-associated protein 1 (MTA1) is crucial for the mammalian circadian clock. MTA1 regulates circadian rhythmicity by interacting with CLOCK-BMAL1 and influencing gene transcription and protein modification.

Area of Science:

  • Chronobiology
  • Molecular Biology
  • Cancer Biology

Background:

  • The mammalian circadian clock governs daily physiological rhythms but its molecular mechanisms remain incompletely understood.
  • Metastasis-associated protein 1 (MTA1) is frequently overexpressed in human cancers.

Purpose of the Study:

  • To investigate the role of metastasis-associated protein 1 (MTA1) in the molecular machinery of the mammalian circadian clock.

Main Methods:

  • Genetic knockout of MTA1 in mice.
  • Biochemical analyses of protein interactions and transcriptional regulation.
  • Assessment of circadian rhythmicity under various light conditions.

Main Results:

  • MTA1 knockout mice exhibit disrupted circadian rhythms, including altered free-running periods and entrainment.
  • The CLOCK-BMAL1 heterodimer directly activates MTA1 transcription.
  • MTA1 interacts with CLOCK-BMAL1, promoting transcription of MTA1 and CRY1.
  • MTA1 deacetylates BMAL1 via SIRT1 regulation, impacting the CRY1-mediated negative feedback loop.

Conclusions:

  • MTA1 is an integral component of the circadian clock machinery.
  • MTA1 plays a significant role in maintaining circadian rhythmicity by modulating the positive limb of the clock.
  • These findings reveal a novel function for MTA1 beyond its established role in cancer.

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