p27 transcriptionally coregulates cJun to drive programs of tumor progression.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30877256.
- Also identified by DOI 10.1073/pnas.1817415116 and PMC identifier 6452716.
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Abstract
p27 shifts from CDK inhibitor to oncogene when phosphorylated by PI3K effector kinases. Here, we show that p27 is a cJun coregulator, whose assembly and chromatin association is governed by p27 phosphorylation. In breast and bladder cancer cells with high p27pT157pT198 or expressing a CDK-binding defective p27pT157pT198 phosphomimetic (p27CK-DD), cJun is activated and interacts with p27, and p27/cJun complexes localize to the nucleus. p27/cJun up-regulates <i>TGFB2</i> to drive metastasis in vivo. Global analysis of p27 and cJun chromatin binding and gene expression shows that cJun recruitment to many target genes is p27 dependent, increased by p27 phosphorylation, and activates programs of epithelial-mesenchymal transformation and metastasis. Finally, human breast cancers with high p27pT157 differentially express p27/cJun-regulated genes of prognostic relevance, supporting the biological significance of the work.
Medical subject headings
- Cell Movement
- Cyclin-Dependent Kinase Inhibitor p27
- Epithelial-Mesenchymal Transition
- Gene Expression Regulation, Neoplastic
- Neoplasms
- Proto-Oncogene Proteins c-jun