The cyclin-dependent kinase inhibitor p27(Kip1) interacts with the aryl hydrocarbon receptor and negatively regulates its transcriptional activity

FEBS LETTERS(2022)

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摘要
p27(Kip1) functions to coordinate cell cycle progression through the inhibition of cyclin-dependent kinase (CDK) complexes. p27(Kip1) 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 p27(Kip1) transcription. Here, we report the physical interaction of AhR and p27(Kip1) and show that p27(Kip1) expression negatively regulates AhR-mediated transcription. p27(Kip1) knockout cells display increased AhR nuclear localisation and significantly higher expression of AhR target genes. This work thus identifies new regulatory cross-talk between p27(Kip1) and AhR.
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关键词
aryl hydrocarbon receptor, cyclin-dependent kinase inhibitor, transcriptional regulation, xenobiotics
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