The cyclin-dependent kinase inhibitor p27Kip1 interacts with the aryl hydrocarbon receptor and negatively regulates its transcriptional activity

细胞周期蛋白依赖性激酶抑制剂 p27Kip1 与芳烃受体相互作用并负向调节其转录活性

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作者:Daniel J Elson, Bach D Nguyen, Rhand Wood, Yi Zhang, Veronica Puig-Sanvicens, Siva K Kolluri

Abstract

p27Kip1 functions to coordinate cell cycle progression through the inhibition of cyclin-dependent kinase (CDK) complexes. p27Kip1 also exerts distinct activities beyond CDK-inhibition, including functioning as a transcriptional regulator. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with diverse biological roles. The regulatory inputs that control AhR-mediated transcriptional responses are an active area of investigation. AhR was previously established as a direct regulator of p27Kip1 transcription. Here, we report the physical interaction of AhR and p27Kip1 and show that p27Kip1 expression negatively regulates AhR-mediated transcription. p27Kip1 knockout cells display increased AhR nuclear localisation and significantly higher expression of AhR target genes. This work thus identifies new regulatory cross-talk between p27Kip1 and AhR.

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