Loss of p53 function through PAX-mediated transcriptional repression.

Abstract

Direct interactions between the genes that regulate development and those which regulate the cell cycle would provide a mechanism by which numerous biological events could be better understood. We have identified a direct role for PAX5 in the control of p53 transcription. In primary human diffuse astrocytomas, PAX5 expression inversely correlated with p53 expression. The human p53 gene harbours a PAX binding site within its untranslated first exon that is conserved throughout evolution. PAX5 and its paralogues PAX2 and PAX8 are capable of inhibiting both the p53 promoter and transactivation of a p53‐responsive reporter in cell culture. Mutation of the identified binding site eliminates PAX protein binding in vitro and renders the promoter inactive in cells. These data suggest that PAX proteins might regulate p53 expression during development and propose a novel alternative mechanism for tumour initiation or progression, by which loss of p53 function occurs at the transcriptional level.

Functional analysis of the host defense peptide Human Beta Defensin-1: New insight into its potential role in cancer

“…Although PAX2 is typically repressed upon terminal differentiation, in urogenital cancers including prostate cancer it has been shown to be overexpressed (Discenza et al, 2003). In addition, studies have demonstrated that PAX2 expression can stimulate proliferation stimulus, thus serving as a critical component of a multi-step oncogenic transformation process (Stuart et al, 1995). Therefore, PAX2 may offer an advantage for the survival and growth of cancer cells.…”

“…PAX genes function to activate or repress transcription by transactivating the promoter of target genes that regulate cell growth and apoptosis (Margue et al, 2000;Stuart et al, 1995). Unique recognition sequences are contained within the paired domain and activating domains in PAX2 that aid to activate or repress the transcription of specific genes (Havik, et al, 1999).…”

Oxidative stress stimulates IL‐4 and IL‐6 production in mast cells by an APE/Ref‐1‐dependent pathway

“…[12,[15][16][17][18]. Moreover, APE/Ref-1 can bind to negative calcium-responsive elements to cause transcriptional repression and activates p53 DNA-binding activity in vitro [33].…”

Additive effect between NF-κB subunits and p53 protein for transcriptional activation of human p53 promoter

“…The p53 WT-LUC (wild-type p53 promoter luciferase reporter), which contains a 550-bp genomic fragment including the human p53 promoter and exon 1 in front of the luciferase gene, was kindly provided by ET Stuart (Stuart et al, 1995). The PMT2T expression vector encoding the RelA NF-kB subunit was previously described (Bours et al, 1992).…”