Cry:Per heterodimer binds Bmal1:Clock,Npas2 heterodimer

Stable Identifier
R-MMU-508741
Type
Reaction [binding]
Species
Mus musculus
Compartment
General
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Cry:Per heterodimer binds Bmal1:Clock,Npas2 heterodimer

Cry (Cry1 and Cry2) and Per (Per1, Per2) proteins form complex in the cytoplasm where they are phosphorylated by Csnk1d and Csnk1e kinases. Cry:Per complexes appear to form stable complexes with a kinase. Because of the nuclear localization signal of Per, the complexes are translocated to the nucleus where they bind Bmal11:Clock/Npas2 (Arntl:Clock/Npas2) heterodimers and inhibit the transactivation activity of Bmal1:Clock/Npas2.
Cry and Per proteins are themselves transcriptionally activated by Bmal1:Clock/Npas2 thus they participate in a negative loop inhibiting their own synthesis and the synthesis of other targets of Bmal1:Clock/Npas2.
Experiments with two-hybrid interaction and in vitro association show that Cry1, Cry2, and Per2 bind Bmal1 at two different sites on Bmal1. Per2 but not Cry1 or Cry2 binds Clock. Different combinations of Per and Cry proteins in Per:Cry complexes have different inhibitory activities.

Literature References
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Curr Biol 2008
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