PTD-p65-P1 Peptide – Other Categories

The nuclear transcription factor NF-kappaB up regulates gene expression during inflammation and has critical roles in carcinogenesis, anti-apoptosis, invasion, and metastasis. This has led to the search for specific inhibitors of NF-kappaB to help study NF-kappaB for possible treatments for inflammatory diseases and cancer in the future. NF-kappaB is held in an inactive state in the cytoplasm as a heterodimer containing a p65 subunit. Signalling leads to revealing of a hidden nuclear localisation sequence within p65, phosphorylation of p65, and translocation to the nucleus. p65 binds to DNA and ultimately transcription of specific genes. Therefore, finding an inhibitor of the nuclear localisation sequence and phosphorylation of the p65 subunit is an attractive target. A peptide named PTD-p65-P1 was generated from the p65 DNA binding domain mimicking the phosphorylated state, attached to a membrane-translocating peptide sequence generated from antennapedia (PTD). PTD-p65-P1 has been shown to inhibit NF-kappaB binding to DNA in a dose dependent manner. This activity was also known to be specific for NF-kappaB inhibition. The inhibition of NF-kappaB activity by PTD p65-P1 was shown to be effective against a range of stimuli including cigarette smoke, interleukin 1 and hydrogen peroxide which suggests the inhibitor acts on a common step against these stimuli. The presence of PTD p65-P1 inhibits the cytoplasmic p65 subunit phosphorylation or translocation. The reporter genes tested for NF-kappaB activity showed down regulation of gene expression in the presence of PTD-p65-P1 peptide. The evidence is compelling that this peptide could be a suitable model for a selective specific inhibitor of NF-kappaB activity for therapeutic use in the future.