Proteinase inhibitors I and II from potatoes specifically block UV-induced activator protein-1 activation through a pathway that is independent of extracellular signal-regulated kinases, c-Jun N-terminal kinases, and P38 kinase.
Solar UV irradiation is the causal factor for the increasing incidence of human skin carcinomas. The activation of the transcription factor activator protein-1 (AP-1) has been shown to be responsible for the tumor promoter action of UV light in mammalian cells. We demonstrate that proteinase inhibitor I (Inh I) and II (Inh II) from potato tubers, when applied to mouse epidermal JB6 cells, block UV-induced AP-1 activation. The inhibition appears to be specific for UV-induced signal transduction for AP-1 activation, because these inhibitors did not block UV-induced p53 activation nor did they exhibit any significant influence on epidermal growth factor-induced AP-1 transactivation. Furthermore, the inhibition of UV-induced AP-1 activity occurs through a pathway that is independent of extracellular signal-regulated kinases and c-Jun N-terminal kinases as well as P38 kinases. Considering the important role of AP-1 in tumor promotion, it is possible that blocking UV-induced AP-1 activity by Inh I or Inh II may be functionally linked to irradiation-induced cell transformation.
Huang
C
C
The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Ma
W Y
WY
Ryan
C A
CA
Dong
Z
Z
D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002460:Cell Line; D000078404:Epidermal Cells; D004817:Epidermis / Q000528:radiation effects*; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases; D009419:Nerve Tissue Proteins; D010940:Plant Proteins / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D011198:Solanum tuberosum; D018808:Transcription Factor AP-1 / Q000187:drug effects*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D048051:p38 Mitogen-Activated Protein Kinases
D009419:Nerve Tissue Proteins; D010940:Plant Proteins; D011480:Protease Inhibitors; D018808:Transcription Factor AP-1; C034104:proteinase inhibitor II protein, plant; C023578:proteinase inhibitor I (plants); D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases