ArticleScience (New York, N.Y.)2019
p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition.
Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
136 citing papers in PubMed, 1 synthesis or guideline pooled it, 233 citations in OpenAlex.
- The Prognostic Role of Cyclin D1 in Multiple Myeloma: A Systematic Review and Meta-Analysis.Technology in cancer research & treatmentPooled it
- Models of Early Resistance to CDK4/6 Inhibitors Unveil Potential Therapeutic Treatment Sequencing.International journal of molecular sciences · 2025Trial
- Cyclins and Cyclin-Dependent Kinases: Structure, Biological Functions, and Innovative Targeting Strategies in Cancer.MedComm · 2026Review
- Adaptive mechanisms and emerging cancer therapeutics for CDK2 inhibitors.Nature chemical biology · 2026Review
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
- WITHDRAWN: From CDK4/6 to CDK2 and KAT: Evolving therapeutic approaches in HR+/HER2- breast cancer.Breast (Edinburgh, Scotland) · 2026Article
- Gomisin G Inhibits Pancreatic Cancer Cell Growth by Promoting YAP Degradation.Food science & nutrition · 2026Article
- AI-Assisted Identification of a Putative Allosteric Ligand Targeting the CDK4/Cyclin D1 Protein-Protein Interface.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Ubiquitin-dependent degradation of p27Kip1 and p21Waf1/Cip1 by AMBRA1 ensures G1 and S phase progression and limits replication stress.Nucleic acids research · 2026Article
- Article
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Stabilization of cyclin D3 protein by CDKN1A (p21Cell communication and signaling : CCS · 2026Article
- Cyclin-E/A/CDK1/2 Kinetic Landscapes Drive Cell Cycle Phase-Specific Progression and Guide Cyclin-E Degradation Strategy.Journal of chemical information and modeling · 2026Article
- Uncovering cancer dependencies in peptide-interacting protein pockets.bioRxiv : the preprint server for biology · 2026Article
- p27Kip1 regulates γ-globin production.Blood · 2026Article
- Bacterial ubiquitin ligase engineered for small molecule and protein target identification.The EMBO journal · 2026Article
- CDK2 inhibitor BLU-222 synergizes with CDK4/6 inhibitors in drug resistant breast cancers through p21/p27 induction.Nature communications · 2026Article
- G1/S arrest: a key mechanism of cellular aging and replicative senescence.Biogerontology · 2026Review
- Genome-wide screenings identify BAP1 as a synthetic-lethality target with CDK4/6 inhibitors.Science advances · 2026Article
76 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The p27 protein is a canonical negative regulator of cell proliferation and acts primarily by inhibiting cyclin-dependent kinases (CDKs). Under some circumstances, p27 is associated with active CDK4, but no mechanism for activation has been described. We found that p27, when phosphorylated by tyrosine kinases, allosterically activated CDK4 in complex with cyclin D1 (CDK4-CycD1). Structural and biochemical data revealed that binding of phosphorylated p27 (phosp27) to CDK4 altered the kinase adenosine triphosphate site to promote phosphorylation of the retinoblastoma tumor suppressor protein (Rb) and other substrates. Surprisingly, purified and endogenous phosp27-CDK4-CycD1 complexes were insensitive to the CDK4-targeting drug palbociclib. Palbociclib instead primarily targeted monomeric CDK4 and CDK6 (CDK4/6) in breast tumor cells. Our data characterize phosp27-CDK4-CycD1 as an active Rb kinase that is refractory to clinically relevant CDK4/6 inhibitors.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.