ArticleMolecular and cellular biology2008
Phosphorylation of p27Kip1 regulates assembly and activation of cyclin D1-Cdk4.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Prognostic significance of p27 in colorectal cancer: a meta-analysis and bioinformatics analysis.Frontiers in oncology · 2024Pooled it
- Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- CDKN1B (p27/kip1) enhances drug-tolerant persister CTCs by restricting polyploidy following mitotic inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- p27Cells · 2025Article
- C-terminally phosphorylated p27 activates self-renewal driver genes to program cancer stem cell expansion, mammary hyperplasia and cancer.Nature communications · 2024Article
- CIP/KIP and INK4 families as hostages of oncogenic signaling.Cell division · 2024Review
- Cryo-EM structure of SKP1-SKP2-CKS1 in complex with CDK2-cyclin A-p27KIP1.Scientific reports · 2023Article
- Article
- CDK4: a master regulator of the cell cycle and its role in cancer.Genes & cancer · 2022Review
- Genetic Drivers of Ileal Neuroendocrine Tumors.Cancers · 2021Review
- p27Cells · 2021Review
- A cancer-associated CDKN1B mutation induces p27 phosphorylation on a novel residue: a new mechanism for tumor suppressor loss-of-function.Molecular oncology · 2021Article
- Unraveling the Molecular Tumor-Promoting Regulation of Cofilin-1 in Pancreatic Cancer.Cancers · 2021Article
- Role of Small GTPase RhoA in DNA Damage Response.Biomolecules · 2021Review
- A unified model for the G1/S cell cycle transition.Nucleic acids research · 2020Review
- Release from cell cycle arrest with Cdk4/6 inhibitors generates highly synchronized cell cycle progression in human cell culture.Open biology · 2020Article
- Genomic competition for noise reduction shaped evolutionary landscape of mir-4673.NPJ systems biology and applications · 2020Article
- MiR-23a-3p promoted G1/S cell cycle transition by targeting protocadherin17 in hepatocellular carcinoma.Journal of physiology and biochemistry · 2020Article
- Regulatory Role of Hexokinase 2 in Modulating Head and Neck Tumorigenesis.Frontiers in oncology · 2020Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
p27 mediates Cdk2 inhibition and is also found in cyclin D1-Cdk4 complexes. The present data support a role for p27 in the assembly of D-type cyclin-Cdk complexes and indicate that both cyclin D1-Cdk4-p27 assembly and kinase activation are regulated by p27 phosphorylation. Prior work showed that p27 can be phosphorylated by protein kinase B/Akt (PKB/Akt) at T157 and T198. Here we show that PKB activation and the appearance of p27pT157 and p27pT198 precede p27-cyclin D1-Cdk4 assembly in early G(1). PI3K/PKB inhibition rapidly reduced p27pT157 and p27pT198 and dissociated cellular p27-cyclin D1-Cdk4. Mutant p27 allele products lacking phosphorylation at T157 and T198 bound poorly to cellular cyclin D1 and Cdk4. Cellular p27pT157 and p27pT198 coprecipitated with Cdk4 but were not detected in Cdk2 complexes. The addition of p27 to recombinant cyclin D1 and Cdk4 led to cyclin D1-Cdk4-p27 complex formation in vitro. p27 phosphorylation by PKB increased p27-cyclin D1-Cdk4 assembly in vitro but yielded inactive Cdk4. In contrast, Src pretreatment of p27 did not affect p27-cyclin D1-Cdk4 complex formation. However, Src treatment led to tyrosine phosphorylation of p27 and catalytic activation of assembled cyclin D1-Cdk4-p27 complexes. Thus, while PKB-dependent p27 phosphorylation appears to increase cyclin D1-Cdk4-p27 assembly or stabilize these complexes in vitro, cyclin D1-Cdk4-p27 activation requires the tyrosine phosphorylation of p27. Constitutive activation of PKB and Abl or Src family kinases in cancers would drive p27 phosphorylation, increase cyclin D1-Cdk4 assembly and activation, and reduce the cyclin E-Cdk2 inhibitory function of p27. Combined therapy with both Src and PI3K/PKB inhibitors may reverse this process.
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