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Cellular overexpression of USP2 enhances PER1-mediated repression on CLOCK/BMAL1 transcriptional activity by promoting PER nuclear retention, and consistently, USP2 knockout mice exhibit increased cytoplasmic PER1 and dampened PER2 and REV-ERB rhythmicity (Yang et al., 2014)

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This suggests that tyrosinase might play a significant role in neuromelanin formation in the human brain and responsible for the neurodegeneration associated with Parkinsons disease and Huntingtons diseases 2226