USP2 Regulates the Intracellular Localization of PER1 and Circadian Gene Expression

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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