Constitutive photomorphogenesis protein 1 (COP1) and COP9 signalosome, evolutionarily conserved photomorphogenic proteins as possible targets of melatonin

The ubiquitin proteasome system has been proposed as a possible mechanism involved in the multiple actions of melatonin. COP 1 (constitutive photomorphogenesis protein 1), a RING finger‐type ubiquitin E 3 ligase formerly identified in A rabidopsis , is a central switch for the transition from plant growth underground in darkness (etiolation) to growth under light exposure (photomorphogenesis). In darkness, COP 1 binds to photomorphogenic transcription factors driving its degradation via the 26 S proteasome; blue light, detected by cryptochromes, and red and far‐red light detected by phytochromes, negatively regulate COP 1. Homologues of plant COP 1 containing all the structural features present in A rabidopsis as well as E 3 ubiquitin ligase activity have been identified in mice and humans. Substrates for mammalian (m) COP 1 include p53, AP ‐1 and c‐ J un, p27 Kip1 , ETV 1, MVP , 14‐3‐3σ, C / EBP α, MTA 1, PEA 3, ACC , TORC 2 and FOXO 1. This m COP 1 target suggests functions related to tumorigenesis, gluconeogenesis, and lipid metabolism. The role of m COP 1 in tumorigenesis (either as a tumor promoter or tumor suppressor), as well as in glucose metabolism (inhibition of gluconeogenesis) and lipid metabolism (inhibition of fatty acid synthesis), has been previously demonstrated. COP 1, along with numerous other ubiquitin ligases, is regulated by the COP 9 signalosome; this protein complex is associated with the oxidative stress sensor K eap1 and the deubiquitinase USP 15. The objective of this review was to provide new information on the possible role of COP 1 and COP 9 as melatonin targets. The hypothesis is based on common functional aspects of melatonin and COP 1 and COP 9, including their dependence on light, regulation of the metabolism, and their control of tumor growth.