ArticleThe EMBO journal2001
p27 cytoplasmic localization is regulated by phosphorylation on Ser10 and is not a prerequisite for its proteolysis.
Article in The EMBO journal, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 287 citations in OpenAlex.
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- Core cell cycle machinery is crucially involved in both life and death of post-mitotic neurons.Cellular and molecular life sciences : CMLS · 2020Review
- Targeting PML in triple negative breast cancer elicits growth suppression and senescence.Cell death and differentiation · 2020Article
- CACYBP Enhances Cytoplasmic Retention of P27Theranostics · 2019Article
- An Insight into the Difficulties in the Discovery of Specific Biomarkers of Limbal Stem Cells.International journal of molecular sciences · 2018Review
- The peptidyl-prolyl isomerase PIN1 relieves cyclin-dependent kinase 2 (CDK2) inhibition by the CDK inhibitor p27.The Journal of biological chemistry · 2017Article
- Deubiquitinating Enzyme USP20 Regulates Extracellular Signal-Regulated Kinase 3 Stability and Biological Activity.Molecular and cellular biology · 2017Article
- Novel interactions of the von Hippel-Lindau (pVHL) tumor suppressor with the CDKN1 family of cell cycle inhibitors.Scientific reports · 2017Article
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- p27eLife · 2017Article
- DCUN1D3 activates SCFSKP2 ubiquitin E3 ligase activity and cell cycle progression under UV damage.Oncotarget · 2016Article
- CRM-1 knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip1.International journal of molecular medicine · 2016Article
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- Regulation of p27American journal of cancer research · 2016Article
- Loss of p27 Associated with Risk for Endometrial Carcinoma Arising in the Setting of Obesity.Current molecular medicine · 2016Article
- Hypoxia inducible prolyl hydroxylase PHD3 maintains carcinoma cell growth by decreasing the stability of p27.Molecular cancer · 2015Article
- p27(Kip1) and Ser10-phosphorylated p27(Kip1) in breast cancer: clinical significance and expression.OncoTargets and therapy · 2015Article
60 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The activity of the cyclin-dependent kinase inhibitor p27 is controlled by its concentration and subcellular localization. However, the mechanisms that regulate its intracellular transport are poorly understood. Here we show that p27 is phosphorylated on Ser10 in vivo and that mutation of Ser10 to Ala inhibits p27 cytoplasmic relocalization in response to mitogenic stimulation. In contrast, a fraction of wild-type p27 and a p27(S10D)-phospho-mimetic mutant translocates to the cytoplasm in the presence of mitogens. G1 nuclear export of p27 and its Ser10 phosphorylation precede cyclin-dependent kinase 2 (Cdk2) activation and degradation of the bulk of p27. Interestingly, leptomycin B-mediated nuclear accumulation accelerates the turnover of endogenous p27; the p27(S10A) mutant, which is trapped in the nucleus, has a shorter half-life than wild-type p27 and the p27(S10D) mutant. In summary, p27 is efficiently degraded in the nucleus and phosphorylation of Ser10 is necessary for the nuclear to cytoplasmic redistribution of a fraction of p27 in response to mitogenic stimulation. This cytoplasmic localization may serve to decrease the abundance of p27 in the nucleus below a certain threshold required for activation of cyclin-Cdk2 complexes.
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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.