PML controls the movement of PER2 into the cell nucleus and affects the body’s internal clock

Loss of the promyelocytic leukaemia (PML) protein disrupts the expression of multiple clock regulators.

• PML is identified as a circadian clock regulator that interacts with the tumour suppressor PER2.
• In the suprachiasmatic nucleus, PML expression and its interaction with PER2 are regulated by the circadian clock.
• Disruption of PML leads to decreased expression of clock genes including Per2, Per1, Cry1, Bmal1, and Npas2.
• The presence of PML and PER2 enhances BMAL1/CLOCK-mediated transcription.
• In cells lacking PML, PER2 primarily localizes to the perinuclear/cytoplasmic regions.
• PML's acetylation status affects PER2's nuclear localization and influences the circadian period in Pml(-/-) mice.

Simplified