A transcriptionally active DNA-binding site for human p53 protein complexes.

Abstract

Recent studies have demonstrated transcriptional activation domains within the tumor suppressor protein p53, while others have described specific DNA-binding sites for p53, implying that the protein may act as a transcriptional regulatory factor. We have used a reiterative selection procedure (CASTing: cyclic amplification and selection of targets) to identify new specific binding sites for p53, using nuclear extracts from normal human fibroblasts as the source of p53 protein.

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…From a large pool of random oligonucleotides, a small subset was selected by the properties of binding to p53 (Funk et al, 1992). The oligomers shared a 20-bp sequence very similar to the consensus sequence, with no intervening sequence between the 10-bp motifs.…”

Targeting gene expression to tumor cells with loss of wild-type p53 function

“…13,[27][28][29] The relevance of this transactivating ability to the tumor suppressor function of p53 is reflected by the fact that ϳ80% of natural genetic changes in TP53 are missense mutations, which are largely confined to its evolutionarily well-conserved and sequence-specific DNA binding central region. 30,31 Furthermore, ϳ30% of mutations are concentrated at several hot spots (e.g., 175r3h, 248r3w, 249r3s, and 273r3h), the original residues of which either directly contact the DNA or preserve the structural integrity of the domain required for DNA binding.…”

A novel gene transfer strategy that combines promoter and transgene activities for improved tumor cell inhibition

“…[14][15][16] Transcriptional activation by p53 is mediated via direct binding to a known DNA motif present in the regulatory elements of target genes. 11,17 P53 also suppresses expression from a variety of promoters, including antiapoptotic control genes, 13,18 the multidrug resistance gene, 19,20 and viral promoters, including the LTRs of HIV, RSV, and HTLV. 21 P53 is known to be a key regulator of apoptosis following radiation or treatment of cells with chemotherapeutic agents such as doxorubicin.…”