| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Hardin, Paul E. Amunugama, Ravi Kim, Eun Young Houl, Jerry H. Ng, Fanny S. Yildirim, Evrim Gunawardhana, Kushan Edery, Isaac Mahesh, Guruswamy Jones, Richard Liu, Yixiao Jeong, Eunhee Allen, David L. |
| Description |
Author Affiliation: Mahesh G ( From the Department of Biology and Center for Biological Clocks Research, Texas A&M University, College Station, Texas 77843.); Jeong E ( the Department of Brain Science, Ajou University School of Medicine, Suwon 443-380, Korea.); Ng FS ( From the Department of Biology and Center for Biological Clocks Research, Texas A&M University, College Station, Texas 77843.); Liu Y ( From the Department of Biology and Center for Biological Clocks Research, Texas A&M University, College Station, Texas 77843.); Gunawardhana K ( From the Department of Biology and Center for Biological Clocks Research, Texas A&M University, College Station, Texas 77843.); Houl JH ( From the Department of Biology and Center for Biological Clocks Research, Texas A&M University, College Station, Texas 77843.); Yildirim E ( the Department of Molecular Biology and Biochemistry, Rutgers University, Center for Advanced Biotechnology and Medicine, Piscataway New Jersey 08854.); Amunugama R ( MS Bioworks, LLC, Ann Arbor, Michigan 48108, and.); Jones R ( MS Bioworks, LLC, Ann Arbor, Michigan 48108, and.); Allen DL ( MS Bioworks, LLC, Ann Arbor, Michigan 48108, and.); Edery I ( the Department of Molecular Biology and Biochemistry, Rutgers University, Center for Advanced Biotechnology and Medicine, Piscataway New Jersey 08854.); Kim EY ( the Department of Brain Science, Ajou University School of Medicine, Suwon 443-380, Korea.); Hardin PE ( From the Department of Biology and Center for Biological Clocks Research, Texas A&M University, College Station, Texas 77843, phardin@bio.tamu.edu.) |
| Abstract |
Circadian (â 24 h) clocks control daily rhythms in metabolism, physiology, and behavior in animals, plants, and microbes. In Drosophila, these clocks keep circadian time via transcriptional feedback loops in which clock-cycle (CLK-CYC) initiates transcription of period (per) and timeless (tim), accumulating levels of PER and TIM proteins feed back to inhibit CLK-CYC, and degradation of PER and TIM allows CLK-CYC to initiate the next cycle of transcription. The timing of key events in this feedback loop are controlled by, or coincide with, rhythms in PER and CLK phosphorylation, where PER and CLK phosphorylation is high during transcriptional repression. PER phosphorylation at specific sites controls its subcellular localization, activity, and stability, but comparatively little is known about the identity and function of CLK phosphorylation sites. Here we identify eight CLK phosphorylation sites via mass spectrometry and determine how phosphorylation at these sites impacts behavioral and molecular rhythms by transgenic rescue of a new Clk null mutant. Eliminating phosphorylation at four of these sites accelerates the feedback loop to shorten the circadian period, whereas loss of CLK phosphorylation at serine 859 increases CLK activity, thereby increasing PER levels and accelerating transcriptional repression. These results demonstrate that CLK phosphorylation influences the circadian period by regulating CLK activity and progression through the feedback loop. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
28 |
| Volume Number |
289 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2014-07-11 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
CLOCK Proteins Metabolism Circadian Rhythm Physiology Drosophila Proteins ARNTL Transcription Factors Genetics Animals Drosophila Melanogaster Period Circadian Proteins Phosphorylation Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
