Nucleocytoplasmic shuttling and mCRY-dependent inhibition of ubiquitylation of the mPER2 clock protein

mPER2 shuttles between the nucleus and cytoplasm, influenced by mCRY proteins.

• The core mechanism for circadian rhythms involves feedback loops where clock gene products inhibit their own expression.
• Nuclear accumulation of mPER2 occurs approximately 6 hours after mRNA expression peaks, and this process is facilitated by mCRY proteins.
• mPER2 is prevented from degradation by the proteasome when retained in the nucleus by mCRY proteins.
• Conversely, mPER2 can prevent the degradation of mCRY proteins, suggesting a reciprocal regulatory relationship.
• The findings support a model where mPER2 is targeted for degradation unless stabilized by its interaction with mCRY proteins.

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