The p53 knowledgebase: an integrated information resource for p53 research

Abstract

The p53 tumor suppressor protein plays a central role in maintaining genomic integrity by occupying a nodal point in the DNA damage control pathway. Here it integrates a wide variety of signals, responding in one of several ways, that is, cell cycle arrest, senescence or programmed cell death (apoptosis). Mutations in the tumor suppressor gene tp53, which affects the key transcriptional regulatory processes in cell growth and death, occur frequently in cancer and helps explain why p53 has been called the guardian of the genome. There is a vast body of published knowledge on all aspects of p53's role in cancer. To facilitate research, it would be helpful if this information could be collected, curated and updated in a format that is easily accessible to the user community. To this end, we initiated the p53 knowledgebase project (http://p53.bii. a-star.edu.sg). The p53 knowledgebase is a user-friendly web portal incorporating visualization and analysis tools that integrates information from the published literature with other manually curated information to facilitate knowledge discovery. This includes curated information on sequence, structural, mutation, polymorphisms, protein-protein interactions, transcription factors, transcriptional targets, antibodies and post-translational modifications that involve p53. The goal is to collect and maintain all relevant data on p53 and present it in an easily accessible format that will be useful to researchers in the field.

Lack of p53 Decreases Basal Oxidative Stress Levels in the Brain Through Upregulation of Thioredoxin-1, Biliverdin Reductase-A, Manganese Superoxide Dismutase, and Nuclear Factor Kappa-B

“…Once activated p53 binds to DNA and transactivates genes encoding proteins responsible for DNA repair, cell cycle arrest, and/or the induction of apoptosis in cells harboring nonrepairable damaged DNA, as well as senescence (42). In this light, it represents a ''guardian'' of genomic integrity preventing the passage of damaged DNA from cell to cell (41).…”

Changing the p53 master regulatory network: ELEMENTary, my dear Mr Watson

“…Although these approaches have been useful for identifying potential sequences that may interact with p53, they do not provide for the in vivo assessment of relative transactivation capability from different REs. Sequence differences and strength of binding have been invoked to explain possible differences in transactivation of groups of genes subject to direct control by p53, as for the case of cell-cycle control versus apoptotic genes (ResnickSilverman et al, 1998;Vousden, 2000;Zhao et al, 2000;Kannan et al, 2001;Qian et al, 2002;Lim et al, 2006).…”

Effect of a natural mutation in the 5′ untranslated region on the translational control of p53 mRNA

“…Interestingly, this particular nucleotide was first reported to have a C-to-T polymorphism in the TP53 gene in human melanoma tumors, 17 and this SNP is mapped to p53 5 0 UTR of reference p53 nucleotide sequence (GenBank accession number X54156) in p53 knowledge base (http://p53.bii.a-star.edu.sg). 18 The evolutionary distances of the p53 cDNAs (as in table, Supplementary Table 2) were represented as an unrooted dendrogram as generated from ClustalW program (Supplementary Figure 3) that reflects the similarities in the p53 cDNA sequences used for the alignment. 3).…”

“…One of these SNPs, C119T, has been reported in human melanoma samples 17 and has been mapped to the 5 0 UTR in p53 knowledge base. 18 Curiously, WT C nucleotide in the 119th position in p53 5 0 UTR has been found to be evolutionarily conserved. Inclusion of SNP2-5 0 UTR in a bicistronic reporter has led to a decrease in the 5 0 UTR IRES activity.…”