Cryptochromes-Mediated Inhibition of the CRL4^Cop1-Complex Assembly Defines an Evolutionary Conserved Signaling Mechanism.

ABSTRACT: In plants, cryptochromes are photoreceptors that negatively regulate the ubiquitin ligase CRL4^Cop1. In mammals, cryptochromes are core components of the circadian clock and repressors of the glucocorticoid receptor (GR). Moreover, mammalian cryptochromes lost their ability to interact with Cop1, suggesting that they are unable to inhibit CRL4^Cop1. Contrary to this assumption, we found that mammalian cryptochromes are also negative regulators of CRL4^Cop1, and through this mechanism, they repress the GR transcriptional network both in cultured cells and in the mouse liver. Mechanistically, cryptochromes inactivate Cop1 by interacting with Det1, a subunit of the mammalian CRL4^Cop1 complex that is not present in other CRL4s. Through this interaction,

SUBMITTER: Rizzini L 

PROVIDER: S-EPMC6581574 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature