Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK.

BMC Molecular Biology
Sonja LangmesserUrs Albrecht

Abstract

Circadian oscillation of clock-controlled gene expression is mainly regulated at the transcriptional level. Heterodimers of CLOCK and BMAL1 act as activators of target gene transcription; however, interactions of PER and CRY proteins with the heterodimer abolish its transcriptional activation capacity. PER and CRY are therefore referred to as negative regulators of the circadian clock. To further elucidate the mechanism how positive and negative components of the clock interplay, we characterized the interactions of PER2, CRY1 and CRY2 with BMAL1 and CLOCK using a mammalian two-hybrid system and co-immunoprecipitation assays. Both PER2 and the CRY proteins were found to interact with BMAL1 whereas only PER2 interacts with CLOCK. CRY proteins seem to have a higher affinity to BMAL1 than PER2. Moreover, we provide evidence that PER2, CRY1 and CRY2 bind to different domains in the BMAL1 protein. The regulators of clock-controlled transcription PER2, CRY1 and CRY2 differ in their capacity to interact with each single component of the BMAL1-CLOCK heterodimer and, in the case of BMAL1, also in their interaction sites. Our data supports the hypothesis that CRY proteins, especially CRY1, are stronger repressors than PER proteins.

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Citations

Feb 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Nicole KuceraEva Wolf
May 27, 2011·The Journal of Biological Chemistry·Rui YeAziz Sancar
Feb 14, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ryan W LoganDipak K Sarkar
Jul 20, 2012·Molecular Medicine·Christos Savvidis, Michael Koutsilieris
Jul 10, 2010·International Journal of Environmental Research and Public Health·Valeriy Zaporozhan, Andriy Ponomarenko
Oct 3, 2013·Journal of Circadian Rhythms·Marie AramendyUrs Albrecht
Mar 7, 2012·Chronobiology International·Melissa Moreira ZanquettaSandra Mara Ferreira Villares
Feb 4, 2016·Nature Communications·Rohit ChavanUrs Albrecht
Aug 18, 2010·Biochimica Et Biophysica Acta·Sanchari GhoshUllas Kolthur-Seetharam
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Jan 27, 2009·Journal of Molecular and Cellular Cardiology·Katsutaka OishiNorio Ishida
Sep 6, 2013·The Journal of Investigative Dermatology·Yusur Al-NuaimiRalf Paus
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Jun 5, 2014·Journal of Molecular Recognition : JMR·Burcu KepsutluSeda Kizilel
Dec 18, 2013·Biochemical and Biophysical Research Communications·Yinghua GaoRuizhe Qian
Sep 9, 2015·Journal of Toxicology·Megan I Mitchell, Anna-Mart Engelbrecht
Sep 21, 2013·Molecular Metabolism·Sylvie ChappuisUrs Albrecht
May 6, 2014·Cell Reports·Makoto AkashiKoichi Node
Sep 10, 2015·PloS One·Qiming Mei, Volodymyr Dvornyk
Jan 10, 2017·Photochemistry and Photobiology·Ibrahim Halil KavakliCihan Aydın
Nov 23, 2016·Biology Open·Rohit ChavanUrs Albrecht
Nov 7, 2019·ELife·Andrea BrennaUrs Albrecht
Apr 8, 2020·International Journal of Molecular Sciences·Yu YangXiming Qin

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Methods Mentioned

BETA
two-hybrid
co-immunoprecipitation
co-immunoprecipitations
immunoprecipitation
transfection
transfections
nuclear translocation
PCR
Protein Assay
immunoprecipitations

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