دورية أكاديمية
The expression of the tumour suppressor HBP1 is down-regulated by growth factors via the PI3K/PKB/FOXO pathway
| العنوان: | The expression of the tumour suppressor HBP1 is down-regulated by growth factors via the PI3K/PKB/FOXO pathway |
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| المؤلفون: | Coomans de Brachène, Alexandra, Bollaert, Emeline, Eijkelenboom, Astrid, de Rocca Serra, Audrey, van der Vos, Kristan E., Burgering, Boudewijn M. T., Coffer, Paul J., Essaghir, Ahmed, Demoulin, Jean-Baptiste |
| المصدر: | Biochemical Journal ; volume 460, issue 1, page 25-36 ; ISSN 0264-6021 1470-8728 |
| بيانات النشر: | Portland Press Ltd. |
| سنة النشر: | 2014 |
| الوصف: | Growth factors inactivate the FOXO (forkhead box O) transcription factors through PI3K (phosphoinositide 3-kinase) and PKB (protein kinase B). By comparing microarray data from multiple model systems, we identified HBP1 (high-mobility group-box protein 1) as a novel downstream target of this pathway. HBP1 mRNA was down-regulated by PDGF (platelet-derived growth factor), FGF (fibroblast growth factor), PI3K and PKB, whereas it was up-regulated by FOXO factors. This observation was confirmed in human and murine fibroblasts as well as in cell lines derived from leukaemia, breast adenocarcinoma and colon carcinoma. Bioinformatics analysis led to the identification of a conserved consensus FOXO-binding site in the HBP1 promoter. By luciferase activity assay and ChIP, we demonstrated that FOXO bound to this site and regulated the HBP1 promoter activity in a PI3K-dependent manner. Silencing of HBP1 by shRNA increased the proliferation of human fibroblasts in response to growth factors, suggesting that HBP1 limits cell growth. Finally, by analysing a transcriptomics dataset from The Cancer Genome Atlas, we observed that HBP1 expression was lower in breast tumours that had lost FOXO expression. In conclusion, HBP1 is a novel target of the PI3K/FOXO pathway and controls cell proliferation in response to growth factors. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1042/bj20131467 |
| الإتاحة: | https://doi.org/10.1042/bj20131467Test https://portlandpress.com/biochemj/article-pdf/460/1/25/678599/bj4600025.pdfTest |
| رقم الانضمام: | edsbas.D05701FC |
| قاعدة البيانات: | BASE |
| DOI: | 10.1042/bj20131467 |
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