p300 Is Involved in the Regulatory Mechanism of EGF-induced CTEN Gene Expression
Date Issued
2015
Date
2015
Author(s)
Liu, Yi-Chou
Abstract
Epidermal growth factor receptor (EGFR) signaling is one of the complex signal transduction pathways. Following EGF stimulation, tensin3 expression is downregulated and CTEN is upregulated, to a level that is sufficient for displacement of tensin3 from integrin. Then tensin3 dissociates from focal adhesion, leading to the breakdown of F-actin and initiation of cell migration in breast cancer. However, the mechanism of EGFR-induced CTEN gene expression is still unclear. Our results have shown that knockdown p300 expression could decrease EGF-induced CTEN mRNA and protein levels in a normal human prostate cell lines, RWPE-1, and a human cervical cancer cell line, HeLa. It indicates that p300 participates in the EGF-regulated CTEN expression. We further demonstrate that after EGF stimulation, p300 is recruited to CTEN promoter through MEK/ERK pathway in HeLa cells, and increases histone acetylation on CTEN promoter to activate CTEN gene expression. EGF also induces the phosphorylation of p300 through MEK/ERK pathway in HeLa cells. Therefore, our study suggests that EGF signaling induces the phosphorylation of p300 through MEK/ERK pathway, thereby enhancing its histone acetyltransferase activity, and in turn recruits an increased level of p300 to CTEN promoter to activate CTEN gene expression.
Subjects
p300
focal adhesion
CTEN
EGF
Tensin
histone modification
SDGs
Type
thesis
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