3 years ago

Stability of Wake-Sleep Cycles Requires Robust Degradation of the PERIOD Protein

Stability of Wake-Sleep Cycles Requires Robust Degradation of the PERIOD Protein
Rongmin Chen, Zachary Jones, Matthew D’Alessandro, Julie Wi, Stephen Beesley, Choogon Lee, Richard Nowakowski, Daniel Vera, Jae Kyoung Kim, Michele Pagano, Kathleen Kyle


Robustness in biology is the stability of phenotype under diverse genetic and/or environmental perturbations. The circadian clock has remarkable stability of period and phase that—unlike other biological oscillators—is maintained over a wide range of conditions. Here, we show that the high fidelity of the circadian system stems from robust degradation of the clock protein PERIOD. We show that PERIOD degradation is regulated by a balance between ubiquitination and deubiquitination, and that disruption of this balance can destabilize the clock. In mice with a loss-of-function mutation of the E3 ligase gene β-Trcp2, the balance of PERIOD degradation is perturbed and the clock becomes dramatically unstable, presenting a unique behavioral phenotype unlike other circadian mutant animal models. We believe that our data provide a molecular explanation for how circadian phases, such as wake-sleep onset times, can become unstable in humans, and we present a unique mouse model to study human circadian disorders with unstable circadian rhythm phases.

Publisher URL: http://www.cell.com/current-biology/fulltext/S0960-9822(17)31317-9

DOI: 10.1016/j.cub.2017.10.014

You might also like
Never Miss Important Research

Researcher is an app designed by academics, for academics. Create a personalised feed in two minutes.
Choose from over 15,000 academics journals covering ten research areas then let Researcher deliver you papers tailored to your interests each day.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.