Biochem Biophys Res Commun. 2007 Mar
16;354(3):769-75PKCepsilon is essential for gelsolin
expression by histone deacetylase inhibitor apicidin in human
cervix cancer cells.
Eun DW, Ahn SH, You JS, Park JW, Lee EK, Lee HN, Kang GM, Lee
JC, Choi WS, Seo DW, Han JW.
College of Pharmacy, Sungkyunkwan University, Suwon 440-746,
Republic of Korea.
Down-regulation of gelsolin expression is associated with
cellular transformation and induction of gelsolin exerts
antitumorigenic effects. In this study, we show that protein
kinase C (PKC) signaling pathway is required for the induction
of gelsolin by the histone deacetylase inhibitor apicidin in
HeLa cells. Apicidin induces gelsolin mRNA independently of the
de novo protein synthesis. Inhibitor study has revealed that the
PKC signaling pathway is involved in the gelsolin expression.
Furthermore, inhibition of PKCepsilon by either siRNA or
dominant-negative mutant completely abrogates the expression of
gelsolin by apicidin, indicating that PKCepsilon is the major
isoform for this process. In parallel, apicidin induction of
gelsolin is antagonized by the inhibition of Sp1 using
dominant-negative Sp1 or specific Sp1 inhibitor mithramycin, and
inhibition of PKC leads to suppression of Sp1 promoter activity.
Our results provide mechanistic insights into molecular
mechanisms of gelsolin induction by apicidin.
PMID: 17257588 |
