The cyclin-dependent kinase inhibitor p27(Kip1) interacts with the aryl hydrocarbon receptor and negatively regulates its transcriptional activity
FEBS LETTERS(2022)
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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