Protein phosphatase 4 may regulate daily body clock by changing CLOCK/BMAL1 activity

Genetic depletion of protein phosphatase 4 (PPP4) shortens the circadian period in human cells.

• Circadian rhythms are regulated by post-translational modifications of clock proteins, with phosphorylation being a key factor.
• Protein phosphatase 4 (PPP4) and its regulatory subunit PPP4R2 are identified as critical components of the circadian system.
• Overexpression of PPP4 lengthens the circadian period, while its depletion has the opposite effect.
• PPP4 inhibits the activity of the CLOCK/BMAL1 complex by binding to BMAL1 and counteracting its phosphorylation.
• This interaction increases CLOCK/BMAL1 DNA occupancy and decreases its transcriptional activity, affecting circadian timing.

Simplified