The expression of the tumor suppressor HBP1 is down-regulated by growthfactors via the PI3K – PKB – FOXO pathway
(2014) Biochemical Journal — Vol. 460, n° 01, p. 25-34 (2014)
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- Growth factors inactivate the Forkhead-box O (FOXO) transcription factors through phosphatidylinositol-3 kinase (PI3K) and protein kinase B (PKB). By comparing microarray data from multiple model systems, we identified the HMG-box protein 1 (HBP1) as a novel downstream target of this pathway. HBP1 mRNA was down-regulated by PDGF, FGF, PI3K and PKB, while it was up-regulated by FOXO factors. This observation was confirmed in human and murine fibroblasts as well as in cell lines derived from leukemia, 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 chromatin immunoprecipitation, we demonstrated that FOXO bound to this site and regulated the HBP1 promoter activity in a PI3K-dependent manner. Silencing of HBP1 by small-hairpin RNA (shRNA) increased human fibroblasts proliferation in response to growth factors, suggesting that HBP1 limits cell growth. Finally, by analyzing a transcriptomics data set from The Cancer Genome Atlas, we observed that HBP1 expression was lower in breast tumors 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
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Coomans de Brachene, A., Bollaert, E., Eijkelenboom, A., de Rocca Serra, A., van der Vos, K., Burgering, B. M. T., Coffer, P., Essaghir, A., & Demoulin, J. B. (2014). The expression of the tumor suppressor HBP1 is down-regulated by growthfactors via the PI3K – PKB – FOXO pathway. Biochemical Journal, 460(01), 25-34. https://doi.org/10.1042/BJ20131467 (Original work published 2014)