ArticleThe Journal of clinical investigation1999
Overexpressed cyclin D3 contributes to retaining the growth inhibitor p27 in the cytoplasm of thyroid tumor cells.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 121 citations in OpenAlex.
- The emerging role of microtubules in invasion plasticity.Frontiers in oncology · 2023Review
- Cyclin D degradation by E3 ligases in cancer progression and treatment.Seminars in cancer biology · 2020Review
- p27kip1 at the crossroad between actin and microtubule dynamics.Cell division · 2019Article
- Expression of p27 and c-Myc by immunohistochemistry in breast ductal cancers in African American women.Annals of diagnostic pathology · 2018Article
- CDK6 protects epithelial ovarian cancer from platinum-induced death via FOXO3 regulation.EMBO molecular medicine · 2017Article
- p27kip1 expression limits H-Ras-driven transformation and tumorigenesis by both canonical and non-canonical mechanisms.Oncotarget · 2016Article
- MicroRNAs in the thyroid.Best practice & research. Clinical endocrinology & metabolism · 2016Review
- Mutant AKT1-E17K is oncogenic in lung epithelial cells.Oncotarget · 2015Article
- Article
- Cyclin-dependent kinase inhibitors, p16 and p27, demonstrate different expression patterns in thymoma and thymic carcinoma.General thoracic and cardiovascular surgery · 2014Article
- Suppression of KIF3B expression inhibits human hepatocellular carcinoma proliferation.Digestive diseases and sciences · 2014Article
- Membrane Proteins Involved in Epithelial-Mesenchymal Transition and Tumor Invasion: Studies on TMPRSS4 and TM4SF5.Genomics & informatics · 2014Review
- Pathogenic mechanisms of deregulated microRNA expression in thyroid carcinomas of follicular origin.Thyroid research · 2011Article
- Phosphorylated p27Kip1 on Thr157 is an important prognosis in human hepatocellular carcinoma in vivo and in vitro.Medical oncology (Northwood, London, England) · 2011Article
- Transcriptional downregulation of p27KIP1 through regulation of E2F function during LMP1-mediated transformation.Journal of virology · 2009Article
- HMGA1a recognition candidate DNA sequences in humans.PloS one · 2009Article
- The tumor suppressor functions of p27(kip1) include control of the mesenchymal/amoeboid transition.Molecular and cellular biology · 2009Article
- TGF-beta through Smad3 signaling stimulates vascular smooth muscle cell proliferation and neointimal formation.American journal of physiology. Heart and circulatory physiology · 2009Article
- Anaplastic thyroid cancer: molecular pathogenesis and emerging therapies.Endocrine-related cancer · 2009Review
- Nucleoporin levels regulate cell cycle progression and phase-specific gene expression.Developmental cell · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The majority of thyroid carcinomas maintain the expression of the cell growth suppressor p27, an inhibitor of cyclin-dependent kinase-2 (Cdk2). However, we find that 80% of p27-expressing tumors show an uncommon cytoplasmic localization of p27 protein, associated with high Cdk2 activity. To reproduce such a situation, a mutant p27 devoid of its COOH-terminal nuclear-localization signal was generated (p27-NLS). p27-NLS accumulates in the cytoplasm and fails to induce growth arrest in 2 different cell lines, indicating that cytoplasm-residing p27 is inactive as a growth inhibitor, presumably because it does not interact with nuclear Cdk2. Overexpression of cyclin D3 may account in part for p27 cytoplasmic localization. In thyroid tumors and cell lines, cyclin D3 expression was associated with cytoplasmic localization of p27. Moreover, expression of cyclin D3 in thyroid carcinoma cells induced cytoplasmic retention of cotransfected p27 and rescued p27-imposed growth arrest. Endogenous p27 also localized prevalently to the cytoplasm in normal thyrocytes engineered to stably overexpress cyclin D3 (PC-D3 cells). In these cells, cyclin D3 induced the formation of cytoplasmic p27-cyclin D3-Cdk complexes, which titrated p27 away from intranuclear complexes that contain cyclins A-E and Cdk2. Our results demonstrate a novel mechanism that may contribute to overcoming the p27 inhibitory threshold in transformed thyroid cells.
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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.