ArticleProceedings of the National Academy of Sciences of the United States of America2015
p27kip1 controls H-Ras/MAPK activation and cell cycle entry via modulation of MT stability.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Review
- Conditional knockout of Dkk3 drives Lgr5+ progenitor reprogramming into hair cells in the mouse cochlea.Theranostics · 2026Article
- Metabolic Alterations in Crassostrea Gigas After Feeding Selenium-Enriched Yeast Based on Transcriptomic Analysis.Biology · 2025Article
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- HMGA1 positively regulates the microtubule-destabilizing protein stathmin promoting motility in TNBC cells and decreasing tumour sensitivity to paclitaxel.Cell death & disease · 2022Article
- p27kip1 expression and phosphorylation dictate Palbociclib sensitivity in KRAS-mutated colorectal cancer.Cell death & disease · 2021Article
- p27Cells · 2021Review
- SOX2 is required independently in both stem and differentiated cells for pituitary tumorigenesis inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- UNC-45A breaks the microtubule lattice independently of its effects on non-muscle myosin II.Journal of cell science · 2021Article
- Dermal Fibroblast Migration and Proliferation Upon Wounding or Lipopolysaccharide Exposure is Mediated by Stathmin.Frontiers in pharmacology · 2021Article
- BRAF Controls the Effects of Metformin on Neuroblast Cell Divisions inInternational journal of molecular sciences · 2020Article
- Regulation of p27Biomolecules · 2020Review
- Isoliquiritigenin inhibits the proliferation, migration and metastasis of Hep3B cells via suppressing cyclin D1 and PI3K/AKT pathway.Bioscience reports · 2020Article
- A non-canonical role for p27Kip1 in restricting proliferation of corneal endothelial cells during development.PloS one · 2020Article
- Article
- UNC-45A Is a Novel Microtubule-Associated Protein and Regulator of Paclitaxel Sensitivity in Ovarian Cancer Cells.Molecular cancer research : MCR · 2019Article
- p27kip1 at the crossroad between actin and microtubule dynamics.Cell division · 2019Article
- UNC-45A is preferentially expressed in epithelial cells and binds to and co-localizes with interphase MTs.Cancer biology & therapy · 2019Article
- PHAP1 promotes glioma cell proliferation by regulating the Akt/p27/stathmin pathway.Journal of cellular and molecular medicine · 2018Article
- Cancer reversion with oocyte extracts is mediated by cell cycle arrest and induction of tumour dormancy.Oncotarget · 2018Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclin-dependent kinase (CDK) inhibitor p27(kip1) is a critical regulator of the G1/S-phase transition of the cell cycle and also regulates microtubule (MT) stability. This latter function is exerted by modulating the activity of stathmin, an MT-destabilizing protein, and by direct binding to MTs. We recently demonstrated that increased proliferation in p27(kip1)-null mice is reverted by concomitant deletion of stathmin in p27(kip1)/stathmin double-KO mice, suggesting that a CDK-independent function of p27(kip1) contributes to the control of cell proliferation. Whether the regulation of MT stability by p27(kip1) impinges on signaling pathway activation and contributes to the decision to enter the cell cycle is largely unknown. Here, we report that faster cell cycle entry of p27(kip1)-null cells was impaired by the concomitant deletion of stathmin. Using gene expression profiling coupled with bioinformatic analyses, we show that p27(kip1) and stathmin conjunctly control activation of the MAPK pathway. From a molecular point of view, we observed that p27(kip1), by controlling MT stability, impinges on H-Ras trafficking and ubiquitination levels, eventually restraining its full activation. Our study identifies a regulatory axis controlling the G1/S-phase transition, relying on the regulation of MT stability by p27(kip1) and finely controlling the spatiotemporal activation of the Ras-MAPK signaling pathway.
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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.