Bax is upregulated by p53 signal pathway in the SPE B-induced apoptosis.
We identify integrin α(v)β(3) and Fas as receptors for the streptococcal pyrogenic exotoxin B (SPE B), and G308S (SPE B mutant, glycine at residue 308 is changed to serine), which interacts with Fas only, in our previous study. Here, we explore the signal pathways that regulate proapoptotic protein expression after SPE B stimulation. We find that both SPE B and G308S can stimulate the serine phosphorylation of p53, and p53 phosphorylation is inhibited by the anti-Fas antibody but not by anti-α(V)β(3) antibody. p38 inhibitor and siRNA decrease the activation and translocation of p53 into the nucleus, which executes its transcription activity. These results indicate that after SPE B treatment, p53 is activated and p38 is the upstream of p53. p38 siRNA also decreases the binding of p53 to the bax promoter and interferes with the association of p53 and STAT1. p53, p38, and STAT1 siRNAs downregulate SPE B-induced Bax expression. This shows that SPE B activates the bax promoter via p38/p53 signal pathways through the Fas receptor, and that STAT1 acts as a coactivator of p53. In addition, p38 and p53 siRNAs inhibit SPE B-induced apoptosis. This is consistent with the findings that SPE B upregulates Bax expression through p38/p53 signal pathways that enhance cell apoptosis.
Lee
Wei-Ting
WT
Department of Otolaryngology, National Cheng Kung University Hospital, Tainan, Taiwan.
Chang
Chia-Wen
CW
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D017931:DNA Primers; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000502:physiology*
D017931:DNA Primers; D050794:STAT1 Transcription Factor; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D003546:Cysteine Endopeptidases; C042477:streptopain