Circadian regulation of c-MYC in mice.

The circadian clock is a global regulatory mechanism that controls the expression of 50 to 80% of transcripts in mammals. Some of the genes controlled by the circadian clock are oncogenes or tumor suppressors. Among these has been the focus of several studies which have investigated the effect of clock genes and proteins on transcription and MYC protein stability. Other studies have focused on effects of mutation or overproduction on the circadian clock in comparison to their effects on cell cycle progression and tumorigenesis. Here we have used mice with mutations in the essential clock genes , and to gain further insight into the effect of the circadian clock on this important oncogene/oncoprotein and tumorigenesis. We find that mutation of both and , which abolishes the negative arm of the clock transcription-translation feedback loop (TTFL), causes down-regulation of c-MYC, and mutation of which abolishes the positive arm of TTFL, causes up-regulation of the c-MYC protein level in mouse spleen. These findings must be taken into account in models of the clock disruption-cancer connection.