FBXL21 controls daily body clock rhythms by tagging and stabilizing key clock proteins

FBXL21 stabilizes CRY proteins and counteracts the degradation mediated by FBXL3.

• FBXL21 and FBXL3 have opposing effects on the regulation of CRY1 and CRY2 proteins, which are crucial for the circadian clock.
• Fbxl21(-/-) mice show normal daily activity patterns but with disorganized behaviors, indicating that FBXL21 plays a role in activity regulation.
• Fbxl3(-/-) mice exhibit an extremely long-period phenotype, which is mitigated in double-knockout mice lacking both FBXL3 and FBXL21.
• The double knockout leads to destabilization of behavioral rhythms and, in some cases, arrhythmicity.
• FBXL21's cytosolic presence contrasts with the nuclear localization of FBXL3, suggesting different functional roles in circadian rhythm regulation.

Simplified