Affiliations: Institute of Molecular and Cell Biology, 61 Biopolis
Drive, Proteos, 138673, Singapore | Bioinformatics Institute, 30 Biopolis Street, Matrix,
138671, Singapore | Department of Biochemistry, Yong Loo Lin School of
Medicine, National University of Singapore, Blk MD7, #02-03, 8 Medical
Drive, 117597, Singapore | Genomics Institute of Singapore, 60 Biopolis Street,
Genome, 138672, Singapore | Bioinformatics Center, National Yang-Ming University,
Taipei, 112, Taiwan
Abstract: P53 is probably the most important tumor suppressor known. Over the
years, information about this gene has increased dramatically. We have built a
comprehensive knowledgebase of p53, which aims to facilitate wet-lab biologists
to formulate their experiments and new-comers to learn whatever they need about
the gene and bioinformaticians to make new discoveries through data analysis.
Using the information curated, including mutation information, transcription
factors, transcriptional targets, and single nucleotide polymorphisms, we have
performed extensive bioinformatics analysis, and made several new discoveries
about P53. We have identified point missense mutations that are
over-represented in cancers, but lack of functional studies. By assessing the
capability of six p53 transcriptional targets' tag SNPs selected from HapMap to
capture SNPs obtained from National Institute of Environmental Health Sciences
(NIEHS) Environmental Genome project and vice versa, we conclude that
NIEHS data is a better source for tagSNP selections of these genes in future
association studies. Analysis of microRNA regulation in the transcriptional
network of the p53 gene reveals potentially important regulatory
relationships between oncogenic microRNAs and transcription factors of
p53. By mapping transcription factors of p53 to pathways involved in
cell cycle and apoptosis, we have identified distinctive transcriptional
controls of p53 in these two physiological states.
