Trichostatin A, a histone deacetylase inhibitor, activates the IGFBP-3 promoter by upregulating Sp1 activity in hepatoma cells: alteration of the Sp1/Sp3/HDAC1 multiprotein complex

Authors
Hong Seok ChoiJe Ho LeeJong Gu ParkYoung Ik Lee
Department
Dept. of Molecular Medicine (분자의학)
Issue Date
2002
Citation
Biochemical and Biophysical Research Communications, Vol.296(4) : 1005-1012, 2002
ISSN
0006-291X
Abstract
We determined the molecular mechanisms by which trichostatin A (TSA) induced insulin-like growth factor-binding protein 3 (IGFBP-3) gene expression in Hep3B cells, a p53-mutant human hepatocellular carcinoma (HCC) cell line. TSA induced the expressions of the IGFBP-3 mRNA and protein and the activation of its promoter. Using IGFBP-3 promoter deletion constructs, the TSA-responsive element was mapped to a region between −115 and −30, relative to the transcription start site. Promoter mutation analysis confirmed that the TSA-responsive element coincides with the Sp1/GC-rich region on the IGFBP-3 promoter. This transcriptional activation appears to be mediated by both the Sp1 and Sp3 transcription factors and, in particular, by the phosphorylation of Sp1, because treatment of Hep3B cells and Schneider (SL2) cells with TSA significantly activated phosphorylation of Sp1 in a dose-dependent manner. Consistent with the transcriptional activation of the IGFBP-3 promoter by TSA, TSA treatment led to the release of HDAC1 and Sp3 from the Sp1 transcriptional factor complex, indicating the involvement of multiprotein complexes containing Sp1, Sp3, p300, and HDAC-1 in IGFBP-3 activation by TSA. Taken together, these results show that Sp1 phosphorylation and the modulation of the Sp1/Sp3/HDAC1 multiprotein complex play a pivotal role in the transcriptional activation of the IGFBP-3 promoter through the Sp1/GC-rich site by TSA. Keywords Trichostatin A; IGF-binding protein-3; Sp1; HDAC1; Phosphorylation; Hepatoma cells; Sp1/GC-rich site; AP2/GA-rich site; Sp1 phosphorylation; Multiprotein complex
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35191
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Molecular Medicine (분자의학)
Keimyung Author(s)
박종구
Full Text
https://linkinghub.elsevier.com/retrieve/pii/S0006291X02020016
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