Structural basis for gene activation by p53 family members

Ariane Scoumanne, Kelly Lynn Harms, Xinbin Chen

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The p53 tumor suppressor is a modular transcription factor that determines cellular outcome (cell cycle arrest and DNA repair vs. apoptosis) in response to stress signals. The two p53 homologues, p63 and p73 play an important role in development but also act as tumor suppressors. The p53 family members are highly homologous in the activation domain (AD), the DNA-binding domain (DBD) and the tetramerization domain (TD) but differ in the C-terminus. Indeed, the p53 C-terminus contains a basic domain (BD) whereas p63/p73 have a sterile α motif (SAM) domain and an inhibitory domain (ID). In addition to the full-length proteins, the p53 family genes produce multiple isoforms truncated at the NH2- and/or C-terminus. Importantly, every functional domain is a determinant in the trans-activation of specific target genes by the p53 family members. Distinct post-translational modifications and interactions with cofactors further modulate the transcriptional activity of the p53 family members in response to particular stress signals. Therefore, divergence in the composition of the p53 family proteins is responsible for the diversity of p53 family functions.

Original languageEnglish (US)
Pages (from-to)1178-1185
Number of pages8
JournalCancer Biology and Therapy
Volume4
Issue number11
StatePublished - Nov 2005
Externally publishedYes

Fingerprint

Transcriptional Activation
p53 Genes
Post Translational Protein Processing
Cell Cycle Checkpoints
DNA Repair
Neoplasms
Protein Isoforms
Proteins
Transcription Factors
Apoptosis
DNA

Keywords

  • Functional domains
  • p53
  • p63
  • p73
  • Post-translational modifications
  • Protein-protein interactions

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Structural basis for gene activation by p53 family members. / Scoumanne, Ariane; Harms, Kelly Lynn; Chen, Xinbin.

In: Cancer Biology and Therapy, Vol. 4, No. 11, 11.2005, p. 1178-1185.

Research output: Contribution to journalArticle

Scoumanne, A, Harms, KL & Chen, X 2005, 'Structural basis for gene activation by p53 family members', Cancer Biology and Therapy, vol. 4, no. 11, pp. 1178-1185.
Scoumanne, Ariane ; Harms, Kelly Lynn ; Chen, Xinbin. / Structural basis for gene activation by p53 family members. In: Cancer Biology and Therapy. 2005 ; Vol. 4, No. 11. pp. 1178-1185.
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