ArticleThe Journal of biological chemistry2012
Tyrosine phosphorylation of the p21 cyclin-dependent kinase inhibitor facilitates the development of proneural glioma.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- The Ongoing Search for Biomarkers of CDK4/6 Inhibitor Responsiveness in Breast Cancer.Molecular cancer therapeutics · 2020Review
- Potential targets of TMEM176A in the growth of glioblastoma cells.OncoTargets and therapy · 2018Article
- ChIP-Seq analysis identifies p27(Kip1)-target genes involved in cell adhesion and cell signalling in mouse embryonic fibroblasts.PloS one · 2017Article
- p27Kip1 and p21Cip1 collaborate in the regulation of transcription by recruiting cyclin-Cdk complexes on the promoters of target genes.Nucleic acids research · 2015Article
- Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.Molecular and cellular biology · 2015Article
- Signal transducer and activator of transcription 5b drives malignant progression in a PDGFB-dependent proneural glioma model by suppressing apoptosis.International journal of cancer · 2015Article
- Signaling through cyclin D-dependent kinases.Oncogene · 2014Review
- Genetic characterization of the role of the Cip/Kip family of proteins as cyclin-dependent kinase inhibitors and assembly factors.Molecular and cellular biology · 2014Article
- The ability of TRIM3 to induce growth arrest depends on RING-dependent E3 ligase activity.The Biochemical journal · 2014Article
- Small double-stranded RNA mediates the anti-cancer effects of p21WAF1/ClP1 transcriptional activation in a human glioma cell line.Yonsei medical journal · 2014Article
- Article
- Assembly, activation, and substrate specificity of cyclin D1/Cdk2 complexes.Biochemistry · 2013Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphorylation of Tyr-88/Tyr-89 in the 3(10) helix of p27 reduces its cyclin-dependent kinase (CDK) inhibitory activity. This modification does not affect the interaction of p27 with cyclin-CDK complexes but does interfere with van der Waals and hydrogen bond contacts between p27 and amino acids in the catalytic cleft of the CDK. Thus, it had been suggested that phosphorylation of this site could switch the tumor-suppressive CDK inhibitory activity to an oncogenic activity. Here, we examined this hypothesis in the RCAS-PDGF-HA/nestin-TvA proneural glioma mouse model, in which p21 facilitates accumulation of nuclear cyclin D1-CDK4 and promotes tumor development. In these tumor cells, approximately one-third of the p21 is phosphorylated at Tyr-76 in the 3(10) helix. Mutation of this residue to glutamate reduced inhibitory activity in vitro. Mutation of this residue to phenylalanine reduced the tumor-promoting activity of p21 in the animal model, whereas glutamate or alanine substitution allowed tumor formation. Consequently, we conclude that tyrosine phosphorylation contributes to the conversion of CDK inhibitors from tumor-suppressive roles to oncogenic roles.
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