Activator mimicry by PP6 regulatory subunits directs Aurora A dephosphorylation in mitosis.

PPP6R2 and PPP6R3 subunits mimic Aurora A activators to direct dephosphorylation, with mutation disrupting binding and increasing spindle-associated Aurora A activity.

• Why it matters: Understanding how PP6 regulatory subunits recognize and regulate Aurora A is crucial for maintaining genome stability during mitosis, yet this mechanism was previously unclear.
• What they did: The study identified a phenylalanine-rich A-box motif in PPP6R2 and PPP6R3 that binds Aurora A, with mutation impairing dephosphorylation and increasing spindle size; additionally, PPP6R2 contains a PLK1-docking site affecting regulation.
• The result: These findings reveal that PP6 subunits mimic Aurora A activators to guide dephosphorylation and show how competitive interactions, such as PLK1 binding, regulate PP6 activity during mitosis.