P73: In silico evidence for a putative third promoter region

A. Emre Sayan, Mario Rossi, Gerry Melino, Richard A. Knight

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The TP73 gene, first identified in 1997, encodes the p73 protein, a p53 tumour suppressor homologue. The lack of mutations in the TP73 gene in cancers and the developmentally abnormal phenotype of the TP73 knockout mouse suggest a different function for TP73 gene derived proteins. An alternative promoter in the third intron of the TP73 gene, which produces a transcription deficient and dominant negative protein (ΔNp73), produces increased complexity in the function of p73 proteins. Functional studies of transcriptionally active (TAp73; regulated by the first promoter) and ΔNp73 (regulated by the second promoter) show that the TP73 gene encodes both a candidate tumour suppressor (TAp73) and an oncogene (ΔNp73), with pro-apoptotic and anti-apoptotic properties, respectively. This "two in one" gene architecture leads us to make an in silico search for other probable promoter regions and transcription start sites in different introns of the TP73 gene. To identify such regulatory regions, we have analysed the genomic structure of human and mouse TP73 genes. We have found introns 1 and 4 to be extremely large and relatively conserved in size in mouse and human, in addition to intron 3, which includes the ΔNp73 promoter. We have further characterized these introns by transcription factor binding motifs, transcription initiation sites, open reading frames, and splicing using six programs that can successfully identify the already characterized promoters. Our results suggest the presence of a candidate 2kbp genomic DNA in the first intron of human TP73 gene, harbouring 2 putative promoter regions, together with a similar region within intron 1 of the mouse gene.

Original languageEnglish
Pages (from-to)765-770
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume313
Issue number3
DOIs
Publication statusPublished - Jan 16 2004

Fingerprint

Genetic Promoter Regions
Computer Simulation
Introns
Genes
Transcription Initiation Site
Tumors
Proteins
Nucleic Acid Regulatory Sequences
Neoplasm Genes
Oncogenes
Knockout Mice
Open Reading Frames
Transcription
Neoplasms
Transcription Factors
Phenotype
Mutation
DNA

Keywords

  • Apoptosis
  • Genomic organization
  • p73
  • Promoter region

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

P73 : In silico evidence for a putative third promoter region. / Sayan, A. Emre; Rossi, Mario; Melino, Gerry; Knight, Richard A.

In: Biochemical and Biophysical Research Communications, Vol. 313, No. 3, 16.01.2004, p. 765-770.

Research output: Contribution to journalArticle

Sayan, A. Emre ; Rossi, Mario ; Melino, Gerry ; Knight, Richard A. / P73 : In silico evidence for a putative third promoter region. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 313, No. 3. pp. 765-770.
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