This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yu, W.
Right arrow Articles by Hardin, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yu, W.
Right arrow Articles by Hardin, P. E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, March 2009, p. 1452-1458, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01777-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

DOUBLETIME Plays a Noncatalytic Role To Mediate CLOCK Phosphorylation and Repress CLOCK-Dependent Transcription within the Drosophila Circadian Clock{triangledown}

Wangjie Yu,1 Hao Zheng,1,{dagger} Jeffrey L. Price,2 and Paul E. Hardin1*

Department of Biology and Center for Research on Biological Clocks, Texas A&M University, College Station, Texas 77843,1 School of Biological Sciences, University of Missouri—Kansas City, 5100 Rockhill Rd., Kansas City, Missouri 641102

Received 20 November 2008/ Returned for modification 19 December 2008/ Accepted 4 January 2009

Circadian clocks keep time via gene expression feedback loops that are controlled by time-of-day-specific changes in the synthesis, activity, and degradation of transcription factors. Within the Drosophila melanogaster circadian clock, DOUBLETIME (DBT) kinase is necessary for the phosphorylation of PERIOD (PER), a transcriptional repressor, and CLOCK (CLK), a transcriptional activator, as CLK-dependent transcription is being repressed. PER- and DBT-containing protein complexes feed back to repress CLK-dependent transcription, but how DBT promotes PER and CLK phosphorylation and how PER and CLK phosphorylation contributes to transcriptional repression have not been defined. Here, we show that DBT catalytic activity is not required for CLK phosphorylation or transcriptional repression and that PER phosphorylation is dispensable for repressing CLK-dependent transcription. These results support a model in which DBT plays a novel noncatalytic role in recruiting additional kinases that phosphorylate CLK, thereby repressing transcription. A similar mechanism likely operates in mammals, given the conserved activities of PER, DBT, and CLK orthologs.

* Corresponding author. Mailing address: Department of Biology and Center for Research on Biological Clocks, Texas A&M University, College Station, TX 77843. Phone: (979) 458-4478. Fax: (979) 845-2891. E-mail: phardin{at}mail.bio.tamu.edu

{triangledown} Published ahead of print on 12 January 2009.

{dagger} Present address: Shanghai Hengrui Pharmaceutical Co., 279 Wenjing Rd., Shanghai 200245, People's Republic of China.

Molecular and Cellular Biology, March 2009, p. 1452-1458, Vol. 29, No. 6
0270-7306/09/$08.00+0     doi:10.1128/MCB.01777-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hung, H.-C., Maurer, C., Zorn, D., Chang, W.-L., Weber, F. (2009). Sequential and Compartment-specific Phosphorylation Controls the Life Cycle of the Circadian CLOCK Protein. J. Biol. Chem. 284: 23734-23742 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»