@article{d0e7d80749e342418f4f585962dace74,
title = "Cost-effective circadian mechanism: rhythmic degradation of circadian proteins spontaneously emerges without rhythmic post-translational regulation",
abstract = "Circadian protein oscillations are maintained by the lifelong repetition of protein production and degradation in daily balance. It comes at the cost of ever-replayed, futile protein synthesis each day. This biosynthetic cost with a given oscillatory protein profile is relievable by a rhythmic, not constant, degradation rate that selectively peaks at the right time of day but remains low elsewhere, saving much of the gross protein loss and of the replenishing protein synthesis. Here, our mathematical modeling reveals that the rhythmic degradation rate of proteins with circadian production spontaneously emerges under steady and limited activity of proteolytic mediators and does not necessarily require rhythmic post-translational regulation of previous focus. Additional (yet steady) post-translational modifications in a proteolytic pathway can further facilitate the degradation's rhythmicity in favor of the biosynthetic cost saving. Our work is supported by animal and plant circadian data, offering a generic mechanism for potentially widespread, time-dependent protein turnover.",
keywords = "In silico biology, Mathematical biosciences, Systems biology",
author = "Roktaek Lim and Junghun Chae and Somers, {David E.} and Ghim, {Cheol Min} and Kim, {Pan Jun}",
note = "Funding Information: We thank {\'A}ron Szab{\'o} for kindly providing the TIM abundance data for our analysis and Jonathan W. Johnson for preparing the graphical abstract. We also thank Liming Xiong, Hang-Hyun Jo, and Zhu Yang for useful information and discussions. This work was supported by Hong Kong Baptist University , Research Committee, Start-up Grant for New Academics (R.L. and P.-J.K.) and the National Research Foundation of Korea Grants NRF-2020R1A4A1019140 funded by the Ministry of Science and ICT (J.C. and C.-M.G). This work was partially conducted with the resources of the High Performance Cluster Computing Centre, Hong Kong Baptist University, which receives funding from Research Grant Council, University Grant Committee of the HKSAR and Hong Kong Baptist University. We also acknowledge the support of the UNIST Supercomputing Center for the computing resources. Funding Information: We thank ?ron Szab? for kindly providing the TIM abundance data for our analysis and Jonathan W. Johnson for preparing the graphical abstract. We also thank Liming Xiong, Hang-Hyun Jo, and Zhu Yang for useful information and discussions. This work was supported by Hong Kong Baptist University, Research Committee, Start-up Grant for New Academics (R.L. and P.-J.K.) and the National Research Foundation of Korea Grants NRF-2020R1A4A1019140 funded by the Ministry of Science and ICT (J.C. and C.-M.G). This work was partially conducted with the resources of the High Performance Cluster Computing Centre, Hong Kong Baptist University, which receives funding from Research Grant Council, University Grant Committee of the HKSAR and Hong Kong Baptist University. We also acknowledge the support of the UNIST Supercomputing Center for the computing resources. C.-M.G. and P.-J.K. supervised the research. R.L. J.C. C.-M.G. and P.-J.K. designed the research. R.L. and J.C. performed the research. R.L. J.C. D.E.S. C.-M.G. and P.-J.K. analyzed the data and wrote the manuscript. The authors declare no competing interests. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = jul,
day = "23",
doi = "10.1016/j.isci.2021.102726",
language = "English",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "7",
}