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DomainsEdit

The p53 protein is composed of several domains: the transactivation domain, a proline rich domain, a central DNA-binding domain, a nuclear export domain, an oligomerization domain, and a nuclear localization signaling domain in the C-terminus of the protein.

The amino-terminus (residues 1-44) contains a transactivation domain, which is responsible for the activation of target genes downstream of the promoter.

The proline-rich domain (residues 58-101) is important for the regulation of the response to DNA damage through apoptosis.

The central DNA-binding domain (residues 102-292) is a core domain containing several structural motifs. The DNA-binding domain (DBD) is the main target of p53 mutations; mutant p53-DBDs are found in over half of all human cancers (Harris, 1993).

The oligomerization domain (residues 325-356), which is responsible for the tetramerization of p53. 

Two nuclear export signals (NES), which are located in the transactivation domain and in the oligomerization domain, respectively. It has been suggested that the tetramerization of p53 may actually mask the NES within the oligomerization domain, allowing nuclear retention.

The nuclear localization signaling (NLS) domain, composed of three nuclear localization signals located in the C-terminus.

Structural MotifsEdit

The p53 DNA-binding domain (DBD) contains a variety of motifs that contribute to p53 binding and function.

The most important motif present in the DBD is the p53 consensus motif. In order for p53-DNA binding to occur, the consensus motif must be present within the enhancer sequence influencing the transcription of the downstream gene of interest (El-Diery et al. 1993). The motif is a specific 20bp consensus sequence consisting of two 10bp half-sites (5'-PuPuPuC(A/T)(T/A)GPyPyPy-3'), which are separated by spacers up to 13 bps long (El-Diery et al. 1993). Depending on their length, these spacers can greatly affect p53 binding affinity. Efficient p53 binding can only occur in the presence of both copies of the 10bp half-site sequence.



SourcesEdit

PagesEdit

  1. Keri: p53: Introduction
  2. Keri: p53: Biological function
  3. Keri: p53: Biosynthesis
  4. Keri: p53: Gene sequence
  5. Keri: p53: Amino acid sequence and composition
  6. Keri: p53: Secondary and tertiary structure
  7. Keri: p53: Domains and structural motifs
  8. Keri: p53: Interactions with macromolecules and small molecules
  9. Keri: p53: Molecular biodiversity and evolution
  10. Keri: p53: Literature overview
  11. Keri: p53: Useful online resources

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