Pin1 acts as a negative regulator of the G2/M transition by interacting with the Aurora-A-Bora complex

Pin1 was the first prolyl isomerase identified that is involved in cell division. The mechanism how Pin1 acts as a negative regulator of mitotic activity in G2 phase remains unclear. In our present study, we found that Aurora A can interact with and phosphorylate Pin1 at Ser16, which suppresses the G2/M function of Pin1 by disrupting its binding ability and mitotic entry. Our results also show that phosphorylation at Ser274 and Ser278 of hBora is critical for Pin1 binding. Through the interaction, Pin1 can alter the cytoplasmic translocation of hBora and promote premature degradation by β-TrCP, which results in a mitotic entry delay. Together with the results that Pin1 protein levels do not significantly fluctuate during cell-cycle progression and Aurora A suppresses the Pin1 G2/M function, our current data demonstrate that a gain of Pin1 function can override the Aurora A-mediated functional suppression of Pin1. Collectively, these results highlight the physiological significance of Aurora A-mediated Pin1 Ser16 phosphorylation for mitotic entry and the suppression of Pin1 is functionally linked to the regulation of mitotic entry via the Aurora A/hBora complex.