P73 in cancer

Alessandro Rufini, Massimiliano Agostini, Francesca Grespi, Richard Tomasini, Berna S. Sayan, Maria Victoria Niklison-Chirou, Franco Conforti, Tania Velletri, Antonio Mastino, Tak W. Mak, Gerry Melino, Richard A. Knight

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

p73 is a tumor suppressor belonging to the p53 family of transcription factors. Distinct isoforms are transcribed from the p73 locus. The use of 2 promoters at the N-terminus allows the expression of an isoform containing (TAp73) or not containing (ΔNp73) a complete N-terminal transactivation domain, with the latter isoform capable of a dominant negative effect over the former. In addition, both N-terminal variants are alternatively spliced at the C-terminus. TAp73 is a bona fide tumor suppressor, being able to induce cell death and cell cycle arrest; conversely, ΔNp73 shows oncogenic properties, inhibiting TAp73 and p53 functions. Here, we discuss the latest findings linking p73 to cancer. The generation of isoform specific null mice has helped in dissecting the contribution of TA versus ΔNp73 isoforms to tumorigenesis. The activity of both isoforms is regulated transcriptionally and by posttranslational modification. p73 dysfunction, particularly of TAp73, has been associated with mitotic abnormalities, which may lead to polyploidy and aneuploidy and thus contribute to tumorigenesis. Although p73 is only rarely mutated in cancer, the tumor suppressor actions of TAp73 are inhibited by mutant p53, a finding that has important implications for cancer therapy. Finally, we discuss the expression and role of p73 isoforms in human cancer, with a particular emphasis on the neuroblastoma cancer model. Broadly, the data support the hypothesis that the ratio between TAp73 and ΔNp73 is crucial for tumor progression and therapeutic response.

Original languageEnglish
Pages (from-to)491-502
Number of pages12
JournalGenes and Cancer
Volume2
Issue number4
DOIs
Publication statusPublished - Apr 2011

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Protein Isoforms
Neoplasms
Carcinogenesis
Polyploidy
Aneuploidy
Post Translational Protein Processing
Cell Cycle Checkpoints
Neuroblastoma
Transcriptional Activation
Cell Death
Transcription Factors
Therapeutics

Keywords

  • knockout mice
  • mitosis
  • mutant p53
  • neuroblastoma
  • p73
  • rhabdomyosarcoma

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Rufini, A., Agostini, M., Grespi, F., Tomasini, R., Sayan, B. S., Niklison-Chirou, M. V., ... Knight, R. A. (2011). P73 in cancer. Genes and Cancer, 2(4), 491-502. https://doi.org/10.1177/1947601911408890

P73 in cancer. / Rufini, Alessandro; Agostini, Massimiliano; Grespi, Francesca; Tomasini, Richard; Sayan, Berna S.; Niklison-Chirou, Maria Victoria; Conforti, Franco; Velletri, Tania; Mastino, Antonio; Mak, Tak W.; Melino, Gerry; Knight, Richard A.

In: Genes and Cancer, Vol. 2, No. 4, 04.2011, p. 491-502.

Research output: Contribution to journalArticle

Rufini, A, Agostini, M, Grespi, F, Tomasini, R, Sayan, BS, Niklison-Chirou, MV, Conforti, F, Velletri, T, Mastino, A, Mak, TW, Melino, G & Knight, RA 2011, 'P73 in cancer', Genes and Cancer, vol. 2, no. 4, pp. 491-502. https://doi.org/10.1177/1947601911408890
Rufini A, Agostini M, Grespi F, Tomasini R, Sayan BS, Niklison-Chirou MV et al. P73 in cancer. Genes and Cancer. 2011 Apr;2(4):491-502. https://doi.org/10.1177/1947601911408890
Rufini, Alessandro ; Agostini, Massimiliano ; Grespi, Francesca ; Tomasini, Richard ; Sayan, Berna S. ; Niklison-Chirou, Maria Victoria ; Conforti, Franco ; Velletri, Tania ; Mastino, Antonio ; Mak, Tak W. ; Melino, Gerry ; Knight, Richard A. / P73 in cancer. In: Genes and Cancer. 2011 ; Vol. 2, No. 4. pp. 491-502.
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