CRY arrests Cop1 to regulate circadian rhythms in mammals

Abstract

Cryptochromes (CRYs) are UVA and blue light photoreceptors present in all major evolutionary lineages ranging from cyanobacteria to plants and animals, including mammals. In plants, blue light activates CRYs to induce photomorphogenesis by inhibiting the CRL4Cop1 E3 ligase complex which regulates the degradation of critical transcription factors involved in plant development and growth. However, in mammals, CRYs do not physically interact with Cop1, and of course mammals are not photomorphogenic, leading to the belief that the CRY–Cop1 axis is not conserved in mammals. This belief was recently overturned by Rizzini et al., who showed that although mammalian CRYs do not inhibit Cop1 activity in a light-dependent manner, they antagonize Cop1 activity by displacing Cop1 from CRL4 E3 ligase complex. Because CRYs oscillate, they act in a circadian manner resulting in daily oscillations in Cop1 substrates and the downstream pathways that they regulate. The conserved antagonism of Cop1 by CRY indicates that the CRY–Cop1 axis has an ancient origin, and was repurposed by evolution to regulate photomorphogenesis in plants and circadian rhythms in mammals.