Inhibition of atypical PKC blocks ultraviolet-induced AP-1 activation by specifically inhibiting ERKs activation

Chuanshu Huang, Jingxia Li, Nanyue Chen, Wei-Ya Ma, G. Tim Bowden, Zigang Dong

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Since ultraviolet (UV) radiation is a major etiologic factor in the development of human skin cancers, investigating the signal transduction pathways initiated by UV radiation may help with the understanding of the molecular mechanisms of UV-induced carcinogenesis. Our previous studies demonstrated that UV-induced activator protein-1 (AP-1) activation is blocked by dominant negative atypical PKCs (aPKCs). Here we investigated the role of aPKC in UV-induced activation of mitogen activated protein (MAP) kinase family members which are considered to be the mediators of AP-1 activation. We found that UV radiation led to translocation of protein kinase C (PKC) ζ and activation of MAP kinase family members as well as an increase of AP-1- dependent transcription activation at the same dose range. Pretreatment of cells or mouse skin with antisense oligonucleotides of PKCζ impaired UV- induced activation of AP-1 in JB6 cells as well as in AP-1-luciferase transgenic mice. It also inhibited UV-induced activation of ERKs but not of JNK and p38 kinases in JB6 cells. In contrast, no significant inhibition of AP-1 activation and MAP kinase activation were observed in cells treated with sense oligonucleotides of PKCζ. Furthermore, overexpression of a dominant negative mutant of PKCλ/ι specifically inhibited activation of extracellular signal-regulated protein kinases (ERKs) but not of c-jun N- terminal kinases (JNKs) nor p38 kinases induced by UV radiation. These results demonstrated that inhibition of aPKC impairs UV-induced AP-1 activation via suppression of ERKs activation but not of JNKs or p38 kinase activation. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)65-75
Number of pages11
JournalMolecular Carcinogenesis
Volume27
Issue number2
DOIs
StatePublished - 2000

Keywords

  • A typical protein kinase C
  • C-jun N- terminal kinase
  • Extracellular signal-regulated protein kinase
  • P38 kinase
  • Ultraviolet

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