ArticleOncogene2006
Negative cell cycle regulator 14-3-3sigma stabilizes p27 Kip1 by inhibiting the activity of PKB/Akt.
Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
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- Kaiso phosphorylation at threonine 606 leads to its accumulation in the cytoplasm, reducing its transcriptional repression of the tumour suppressor CDH1.Molecular oncology · 2022Article
- Review
- Correlation of constitutive photomorphogenic 1 (COP1) and p27 tumor suppressor protein expression in ovarian cancer.Genes & genomics · 2019Article
- RBL2/p130 is a direct AKT target and is required to induce apoptosis upon AKT inhibition in lung cancer and mesothelioma cell lines.Oncogene · 2018Article
- iTRAQ-based quantitative proteomic analysis of differentially expressed proteins in chemoresistant nasopharyngeal carcinoma.Cancer biology & therapy · 2018Article
- Regulation of p27American journal of cancer research · 2016Article
- Elevated expression of long intergenic non-coding RNA HOTAIR in a basal-like variant of MCF-7 breast cancer cells.Molecular carcinogenesis · 2015Article
- COP1 enhances ubiquitin-mediated degradation of p27Kip1 to promote cancer cell growth.Oncotarget · 2015Article
- Construction of phosphorylation interaction networks by text mining of full-length articles using the eFIP system.Database : the journal of biological databases and curation · 2015Article
- Regulating the stability and localization of CDK inhibitor p27(Kip1) via CSN6-COP1 axis.Cell cycle (Georgetown, Tex.) · 2015Article
- Cyclin-dependent kinase inhibitors, p16 and p27, demonstrate different expression patterns in thymoma and thymic carcinoma.General thoracic and cardiovascular surgery · 2014Article
- CDK inhibitor p57 (Kip2) is downregulated by Akt during HER2-mediated tumorigenicity.Cell cycle (Georgetown, Tex.) · 2013Article
- HER2-Akt signaling in regulating COP9 signalsome subunit 6 and p53.Cell cycle (Georgetown, Tex.) · 2012Article
- New pyrazolo[3,4-d]pyrimidine SRC inhibitors induce apoptosis in mesothelioma cell lines through p27 nuclear stabilization.Oncogene · 2012Article
- Article
- Roles of COP9 signalosome in cancer.Cell cycle (Georgetown, Tex.) · 2011Review
- 14-3-3 proteins as signaling integration points for cell cycle control and apoptosis.Seminars in cell & developmental biology · 2011Review
- 14-3-3sigma exerts tumor-suppressor activity mediated by regulation of COP1 stability.Cancer research · 2011Article
- Mechanisms of Trastuzumab resistance in ErbB2-driven breast cancer and newer opportunities to overcome therapy resistance.Journal of carcinogenesis · 2011Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The 14-3-3sigma (sigma) protein is a human cancer marker downregulated in various tumors, but its function has not been fully established. 14-3-3sigma is a negative regulator of cell cycle when overexpressed, but it is not clear whether 14-3-3sigma regulates cyclin-dependent kinase inhibitor p27(Kip1) to negatively affect cell cycle progression. Protein kinase B/Akt is a crucial regulator of oncogenic signal and can phosphorylate p27(Kip1) to enhance p27(Kip1)degradation, thereby promoting cell growth. Here, we show that 14-3-3sigma-mediated cell cycle arrest concurred with p27(Kip1) upregulation and Akt inactivation. We show that 14-3-3sigma blocks Akt-mediated acceleration of p27(Kip1) turnover rate. 14-3-3sigma inhibits Akt-mediated p27(Kip1) phosphorylation that targets p27(Kip1) for nuclear export and degradation. 14-3-3sigma inhibits cell survival and tumorigenicity of Akt-activating breast cancer cell. Low expression of 14-3-3sigma in human primary breast cancers correlates with cytoplasmic location of p27(Kip1). These data provide an insight into 14-3-3sigma activity and rational cancer gene therapy by identifying 14-3-3sigma as a positive regulator of p27 and as a potential anticancer agent.
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