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The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon.

Publication ,  Journal Article
Eide, EJ; Vielhaber, EL; Hinz, WA; Virshup, DM
Published in: J Biol Chem
May 10, 2002

The serine/threonine protein kinase casein kinase I epsilon (CKIepsilon) is a key regulator of metazoan circadian rhythm. Genetic and biochemical data suggest that CKIepsilon binds to and phosphorylates the PERIOD proteins. However, the PERIOD proteins interact with a variety of circadian regulators, suggesting the possibility that CKIepsilon may interact with and phosphorylate additional clock components as well. We find that CRY1 and BMAL1 are phosphoproteins in cultured cells. Mammalian PERIOD proteins act as a scaffold with distinct domains that simultaneously bind CKIepsilon and mCRY1 and mCRY2 (mCRY). mCRY is phosphorylated by CKIepsilon only when both proteins are bound to mammalian PERIOD proteins. BMAL1 is also a substrate for CKIepsilon in vitro, and CKIepsilon kinase activity positively regulates BMAL1-dependent transcription from circadian promoters in reporter assays. We conclude that CKIepsilon phosphorylates multiple circadian substrates and may exert its effects on circadian rhythm in part by a direct effect on BMAL1-dependent transcription.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 10, 2002

Volume

277

Issue

19

Start / End Page

17248 / 17254

Location

United States

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Receptors, G-Protein-Coupled
  • Protein Structure, Tertiary
  • Protein Kinases
  • Protein Binding
  • Promoter Regions, Genetic
  • Precipitin Tests
  • Photoreceptor Cells, Invertebrate
 

Citation

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Eide, E. J., Vielhaber, E. L., Hinz, W. A., & Virshup, D. M. (2002). The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon. J Biol Chem, 277(19), 17248–17254. https://doi.org/10.1074/jbc.M111466200
Eide, Erik J., Erica L. Vielhaber, William A. Hinz, and David M. Virshup. “The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon.J Biol Chem 277, no. 19 (May 10, 2002): 17248–54. https://doi.org/10.1074/jbc.M111466200.
Eide EJ, Vielhaber EL, Hinz WA, Virshup DM. The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon. J Biol Chem. 2002 May 10;277(19):17248–54.
Eide, Erik J., et al. “The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon.J Biol Chem, vol. 277, no. 19, May 2002, pp. 17248–54. Pubmed, doi:10.1074/jbc.M111466200.
Eide EJ, Vielhaber EL, Hinz WA, Virshup DM. The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon. J Biol Chem. 2002 May 10;277(19):17248–17254.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

May 10, 2002

Volume

277

Issue

19

Start / End Page

17248 / 17254

Location

United States

Related Subject Headings

  • Transfection
  • Transcription, Genetic
  • Transcription Factors
  • Receptors, G-Protein-Coupled
  • Protein Structure, Tertiary
  • Protein Kinases
  • Protein Binding
  • Promoter Regions, Genetic
  • Precipitin Tests
  • Photoreceptor Cells, Invertebrate