TitleThe cyclin-dependent kinase inhibitor p27 interacts with the aryl hydrocarbon receptor and negatively regulates its transcriptional activity.
Publication TypeJournal Article
Year of Publication2022
AuthorsElson DJ, Nguyen BD, Wood R, Zhang Y, Puig-Sanvicens V, Kolluri SK
JournalFEBS Lett
Volume596
Issue16
Pagination2056-2071
Date Published2022 Aug
ISSN1873-3468
KeywordsCell Cycle Proteins, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases, Gene Expression Regulation, Receptors, Aryl Hydrocarbon
Abstract

p27 functions to coordinate cell cycle progression through the inhibition of cyclin-dependent kinase (CDK) complexes. p27 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 transcription. Here, we report the physical interaction of AhR and p27 and show that p27 expression negatively regulates AhR-mediated transcription. p27 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 and AhR.

DOI10.1002/1873-3468.14434
Alternate JournalFEBS Lett
PubMed ID35735777