ArticleOncogene2010
Regulation of C/EBPbeta1 by Ras in mammary epithelial cells and the role of C/EBPbeta1 in oncogene-induced senescence.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- PAK4 phosphorylates cyclin-dependent kinase 2 to promote the GExperimental & molecular medicine · 2025Article
- Aberrant expression of p16Cancer reports and reviews · 2018Article
- Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.The Journal of steroid biochemistry and molecular biology · 2017Article
- Synergistic drug combinations from electronic health records and gene expression.Journal of the American Medical Informatics Association : JAMIA · 2017Article
- An Arf-Egr-C/EBPβ pathway linked to ras-induced senescence and cancer.Molecular and cellular biology · 2015Article
- Article
- Interaction and cooperation of the CCAAT-box enhancer-binding protein β (C/EBPβ) with the homeodomain-interacting protein kinase 2 (Hipk2).The Journal of biological chemistry · 2013Article
- C/EBPγ suppresses senescence and inflammatory gene expression by heterodimerizing with C/EBPβ.Molecular and cellular biology · 2013Article
- Ras-induced ROS upregulation affecting cell proliferation is connected with cell type-specific alterations of HSF1/SESN3/p21Cip1/WAF1 pathways.Cell cycle (Georgetown, Tex.) · 2013Article
- Oncogenic KRAS impairs EGFR antibodies' efficiency by C/EBPβ-dependent suppression of EGFR expression.Neoplasia (New York, N.Y.) · 2012Article
- Oncogene-induced senescence and its role in tumor suppression.Journal of mammary gland biology and neoplasia · 2011Review
- Antagonistic TSC22D1 variants control BRAF(E600)-induced senescence.The EMBO journal · 2011Article
- Article
- C/EBPβ's role in determining Ras-induced senescence or transformation.Small GTPases · 2011Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Overexpression of Ras(V12) in MCF10A cells, an immortalized mammary epithelial cell line, leads to transformation of these cells. We demonstrate that this is accompanied by degradation of C/EBPbeta1. C/EBPbeta is a transcription factor in which three protein isoforms exist because of alternative translation at three in-frame methionines. When C/EBPbeta1 is expressed in MCF10A-Ras(V12) cells, immunoblot analysis reveals that C/EBPbeta1 is degraded in these cells. Treatment of MCF10A-Ras(V12)-C/EBPbeta1 cells with the cdk inhibitor roscovitine leads to stabilization of C/EBPbeta1. It has been previously shown that cdk2 phosphorylates C/EBPbeta on Thr235. We demonstrate that mutation of Thr235 to alanine in C/EBPbeta1 is sufficient to restore the stability of C/EBPbeta1 expression in MCF10A-Ras(V12) cells. Overexpression of Ras(V12) in primary cells induces senescence rather than transformation, thus suppressing tumorigenesis. C/EBPbeta is required for Ras(V12)-induced senescence in primary mouse embryonic fibroblasts. Upregulation of interleukin-6 (IL6) by C/EBPbeta has been shown to be necessary for oncogene-induced senescence, but the specific isoform of C/EBPbeta has not been investigated. We show that the C/EBPbeta1 isoform upregulates IL6 when introduced into normal fibroblasts. In addition, we show that C/EBPbeta1 induces senescence. Taken together, degradation of C/EBPbeta1 by Ras activation may represent a mechanism to bypass OIS.
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