ArticleMolecular and cellular biology2015
Brk/Protein tyrosine kinase 6 phosphorylates p27KIP1, regulating the activity of cyclin D-cyclin-dependent kinase 4.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Prognostic significance of p27 in colorectal cancer: a meta-analysis and bioinformatics analysis.Frontiers in oncology · 2024Pooled it
- G0 or no-G0: phosphatase control of quiescence and cell cycle entry.Biochemical Society transactions · 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
- Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i): Mechanisms of resistance and where to find them.Breast (Edinburgh, Scotland) · 2025Review
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- Review
- ACK1 upregulated the proliferation of head and neck squamous cell carcinoma cells by promoting p27 phosphorylation and degradation.Journal of cell communication and signaling · 2022Article
- Conserved Cdk inhibitors show unique structural responses to tyrosine phosphorylation.Biophysical journal · 2022Article
- CDK4 and CDK6 kinases: From basic science to cancer therapy.Science (New York, N.Y.) · 2022Review
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
- Monoclonal antibodies to activated CDK4: use to investigate normal and cancerous cell cycle regulation and involvement of phosphorylations of p21 and p27.Cell cycle (Georgetown, Tex.) · 2022Article
- CDK4/6 Inhibitors in Combination Therapies: Better in Company Than Alone: A Mini Review.Frontiers in oncology · 2022Review
- p27kip1 expression and phosphorylation dictate Palbociclib sensitivity in KRAS-mutated colorectal cancer.Cell death & disease · 2021Article
- A cyclin D-CDK6 dimer helps to reshuffle cyclin-dependent kinase inhibitors (CKI) to overcome TGF-beta-mediated arrest and maintain CDK2 activity.Cell cycle (Georgetown, Tex.) · 2021Article
- Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Frontiers in oncology · 2021Review
- Mechanisms of resistance to cyclin-dependent kinase 4/6 inhibitors.Molecular biology reports · 2021Review
- A unified model for the G1/S cell cycle transition.Nucleic acids research · 2020Review
- Targeting protein tyrosine kinase 6 in cancer.Biochimica et biophysica acta. Reviews on cancer · 2020Review
- Release from cell cycle arrest with Cdk4/6 inhibitors generates highly synchronized cell cycle progression in human cell culture.Open biology · 2020Article
- The Ongoing Search for Biomarkers of CDK4/6 Inhibitor Responsiveness in Breast Cancer.Molecular cancer therapeutics · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Cyclin D and cyclin-dependent kinase 4 (cdk4) are overexpressed in a variety of tumors, but their levels are not accurate indicators of oncogenic activity because an accessory factor such as p27(Kip1) is required to assemble this unstable dimer. Additionally, tyrosine (Y) phosphorylation of p27 (pY88) is required to activate cdk4, acting as an "on/off switch." We identified two SH3 recruitment domains within p27 that modulate pY88, thereby modulating cdk4 activity. Via an SH3-PXXP interaction screen, we identified Brk (breast tumor-related kinase) as a high-affinity p27 kinase. Modulation of Brk in breast cancer cells modulates pY88 and increases resistance to the cdk4 inhibitor PD 0332991. An alternatively spliced form of Brk (Alt Brk) which contains its SH3 domain blocks pY88 and acts as an endogenous cdk4 inhibitor, identifying a potentially targetable regulatory region within p27. Brk is overexpressed in 60% of breast carcinomas, suggesting that this facilitates cell cycle progression by modulating cdk4 through p27 Y phosphorylation. p27 has been considered a tumor suppressor, but our data strengthen the idea that it should also be considered an oncoprotein, responsible for cyclin D-cdk4 activity.
Indexed as
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.