title: PKCepsilon is essential for gelsolin expression by histone deacetylase inhibitor apicidin in human cervix cancer cells.
abstract: 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.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Dae-Wook
authors.initials: DW
authors.lastname: Eun
authors.forename: Seong Hoon
authors.initials: SH
authors.lastname: Ahn
authors.forename: Jeong Soo
authors.initials: JS
authors.lastname: You
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Hyun Nah
authors.initials: HN
authors.lastname: Lee
authors.forename: Gil Myoung
authors.initials: GM
authors.lastname: Kang
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Lee
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.forename: Dong-Wan
authors.initials: DW
authors.lastname: Seo
authors.forename: Jeung-Whan
authors.initials: JW
authors.lastname: Han
mesh_terms: D001665:Binding Sites; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009154:Mutation; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*
chemical_list: D004791:Enzyme Inhibitors; D018260:Gelsolin; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C102351:apicidin; D051744:Protein Kinase C-epsilon