Functional role of extracellular signal-regulated kinase activation and c-Jun induction in phorbol ester-induced promoter activation of human 12(S)-lipoxygenase gene

Ben Kuen Chen, Tein Yi Tsai, Huei Sheng Huang, Lei Chin Chen, Wei Chiao Chang, Song Bor Tsai, Wen Chang Chang

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The functional role of mitogen-activated protein kinase (MAPK) signaling and c-Jun induction in phorbol 12-myristate 13-acetate (PMA)-induced human 12(S)-lipoxygenase gene expression was studied in human epidermoid carcinoma A431 cells. Among the family of MAPK, PMA only increased the activity of extracellular signal-regulated kinase (ERK). Treatment of cells with PD98059, which is an inhibitor of mitogen-activated protein kinase kinase (MEK), decreased the PMA-induced expression of 12(S)-lipoxygenase. Transfection of cells with Ras, Raf and ERK2 dominant negative mutants inhibited the PMA-induced promoter activation of the 12(S)-lipoxygenase gene in all cases. PMA-induced expression of c-Jun was inhibited by pretreatment with PD98059. Following treatment with PMA, the interaction between c-Jun and simian virus 40 promoter factor 1 (Sp1) in cells increased with time. Enhancement of binding between the c-Jun-Sp1 complex and the Sp1 oligonucleotide was observed in cells treated with PMA, suggesting the possible interaction of c-Jun-Sp1 with GC-rich binding sites in the gene promoter. These results indicate that PMA treatment induced ERK activation mainly through the Raf-MEK-ERK signaling pathway following induction of c-Jun expression, and the formation of the c-Jun-Sp1 complex. Finally, PMA activated the promoter activity of the 12(S)-lipoxygenase gene in cells overexpressing protein kinase C (PKC)δ but not PKCα, indicating that PKCδ played the functional role in mediating the gene activation of 12(S)-lipoxygenase induced by PMA.

Original languageEnglish
Pages (from-to)156-165
Number of pages10
JournalJournal of Biomedical Science
Volume9
Issue number2
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • 12(S)-Lipoxygenase
  • c-Jun
  • Extracellular signal-regulated kinase
  • Phorbol 12-myristate 13-acetate
  • Sp1

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Functional role of extracellular signal-regulated kinase activation and c-Jun induction in phorbol ester-induced promoter activation of human 12(S)-lipoxygenase gene'. Together they form a unique fingerprint.

  • Cite this