title: Pin1 acts as a negative regulator of the G2/M transition by interacting with the Aurora-A-Bora complex.
abstract: Pin1 was the first prolyl isomerase identified that is involved in cell division. The mechanism by which Pin1 acts as a negative regulator of mitotic activity in G2 phase remains unclear. Here, 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 of Bora at Ser274 and Ser278 is crucial for binding of Pin1. Through the interaction, Pin1 can alter the cytoplasmic translocation of Bora and promote premature degradation by β-TrCP, which results in a delay in mitotic entry. Together with the results that Pin1 protein levels do not significantly fluctuate during cell-cycle progression and Aurora A suppresses Pin1 G2/M function, our 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 through the Aurora-A-Bora complex.
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan.
authors: Yu-Cheng
authors: YC
authors: Lee
authors: Jenny
authors: J
authors: Que
authors: Yu-Chia
authors: YC
authors: Chen
authors: Jen-Tai
authors: JT
authors: Lin
authors: Yih-Cherng
authors: YC
authors: Liou
authors: Po-Chi
authors: PC
authors: Liao
authors: Yu-Peng
authors: YP
authors: Liu
authors: Kuen-Haur
authors: KH
authors: Lee
authors: Li-Ching
authors: LC
authors: Lin
authors: Michael
authors: M
authors: Hsiao
authors: Liang-Yi
authors: LY
authors: Hung
authors: Chi-Ying
authors: CY
authors: Huang
authors: Pei-Jung
authors: PJ
authors: Lu
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002477:Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D015536:Down-Regulation; D016195:G2 Phase; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding
chemical_list: D018797:Cell Cycle Proteins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C528235:bora protein, human; D064096:Aurora Kinase A; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse
keywords: Aurora A; Bora; G2/M negative regulator; Pin1