Regulatory factor X1-induced down-regulation of transforming growth factor β2 transcription in human neuroblastoma cells.

The Journal of Biological Chemistry
Chenzhuo Feng, Zhiyi Zuo

Abstract

Regulatory factor X (RFX) proteins are transcription factors. Seven mammalian RFX proteins have been identified. RFX1 is the prototype RFX. However, its biological functions are not known. Here, RFX1 overexpression reduced fetal bovine serum-stimulated proliferation of SH-SY5Y cells, a human neuroblastoma cell line. This inhibition is associated with decreased transforming growth factor β2 (TGFβ2) and phospho-extracellular signal-regulated kinase (ERK). Exogenous TGFβ2 increased cell proliferation and phospho-ERK in cells overexpressing RFX1. An anti-TGFβ2 antibody and PD98059, an ERK activation inhibitor, inhibited SH-SY5Y cell proliferation. TGFβ2 promoter activity was decreased in cells overexpressing RFX1. Chromosome immunoprecipitation assay showed that RFX1 bound the TGFβ2 promoter. RFX1 down-regulation increased TGFβ2 in SH-SY5Y and HCN-1A cells, a normal human neuronal cell line. More importantly, TGFβ2 concentrations were negatively correlated with RFX1 levels in human medulloblastoma tissues with a R(2) of 0.464. These results suggest that RFX1 reduces cell proliferation through inhibiting the TGFβ2-ERK signaling pathway. RFX1 blocks TGFβ2 expression through its direct action on TGFβ2 transcription. This effect also a...Continue Reading

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Citations

Sep 18, 2012·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Hongyu ZhaoDebao Zhi
Oct 29, 2013·Cellular and Molecular Life Sciences : CMLS·Massimiliano G BianchiOvidio Bussolati
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Jun 30, 2019·Expert Review of Molecular Diagnostics·Shinichi UmedaYasuhiro Kodera
Jul 28, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Kristiina TammimiesPeter Swoboda
May 10, 2021·Cancer Cell International·Joby IssacAni V Das

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