Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells.
Emerging evidence has suggested a critical role for activator protein-1 (AP)-1 in regulating various cellular functions. The goal of this study was to investigate the effects of Helicobacter pylori and mitogen-activated protein kinases (MAPK) on AP-1 subcomponents expression and AP-1 DNA-binding activity in gastric epithelial cells. We found that H. pylori infection resulted in a time- and dose-dependent increase in the expression of the proteins c-Jun, JunB, JunD, Fra-1, and c-Fos, which make up the major AP-1 DNA-binding proteins in AGS and MKN45 cells, while the expression levels of Fra-2 and FosB remained unchanged. Helicobacter pylori infection and MAPK inhibition altered AP-1 subcomponent protein expression and AP-1 DNA-binding activity, but did not change the overall subcomponent composition. Different clinical isolates of H. pylori showed various abilities to induce AP-1 DNA binding. Mutation of cagA, cagPAI, or vacA, and the nonphosphorylateable CagA mutant (cagA(EPISA)) resulted in less H. pylori-induced AP-1 DNA-binding activity, while mutation of the H. pylori flagella had no effect. extracellular signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) each selectively regulated AP-1 subcomponent expression and DNA-binding activity. These results provide more insight into how H. pylori and MAPK modulate AP-1 subcomponents in gastric epithelial cells to alter the expression of downstream target genes and affect cellular functions.
Ding
Song-Ze
SZ
Department of Microbiology, The University of Virginia Health System, 1300 Jefferson Park Avenue, Charlottesville, VA 22908, USA.
Olekhnovich
Igor N
IN
Cover
Timothy L
TL
Peek
Richard M
RM
Smith
Michael F
MF
Goldberg
Joanna B
JB
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology*; D017353:Gene Deletion; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011485:Protein Binding; D018808:Transcription Factor AP-1 / Q000096:biosynthesis*
D001426:Bacterial Proteins; D018808:Transcription Factor AP-1; D004247:DNA; D020928:Mitogen-Activated Protein Kinases