USP2 controls where PER1 is located inside cells and affects daily gene activity

Mice lacking the deubiquitinating enzyme USP2 show advanced rhythms in the nuclear entry of the clock protein PERIOD1 (PER1).

• USP2 is associated with clock proteins and regulates the movement and retention of PER1 in the nucleus.
• The absence of USP2 results in defects in clock function in mice.
• In mouse embryonic fibroblasts without USP2, the timing of PER1's nuclear entry is advanced, but its nuclear accumulation is reduced.
• While the rhythm of Per1 mRNA expression remains unchanged in Usp2 knockout cells, the expression of other core clock genes is altered.
• Similar changes in PER1 nuclear localization and clock gene expression profiles occur in the livers of Usp2 knockout mice.

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