Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop

Fabio Valenti, Francesca Fausti, Francesca Biagioni, Tal Shay, Giulia Fontemaggi, Eytan Domany, Michael B. Yaffe, Sabrina Strano, Giovanni Blandino, Silvia Di Agostino

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Aberrant activation of kinases has emerged to be a key event along with tumor progression, maintenance of tumor phenotype and response to anticancer treatments. This study documents the existence of an oncogenic autoregulatory feedback loop that includes the polo-like kinase-2 (Snk/Plk2) and mutant p53 proteins. Plk2 protein binds to and phosphorylates mutant p53, thereby potentiating its oncogenic activities. Phosphorylated mutant p53 binds more efficiently to p300, consequently strengthening its own transcriptional activity. Plk2 gene is regulated at a transcriptional level by both wt- and mutant p53 proteins. This leads to growth suppression or enhanced cell proliferation and chemoresistance, respectively. In turn, the siRNA-mediated knockdown of either mutant p53 or Plk2 proteins significantly curtails the growth properties of tumor cells and their chemo-resistance to anticancer treatments. Therefore, this paper identifies a novel tumor network including Plk2 and mutant p53 proteins whose triggering in response to DNA damage might disclose important implications for the treatment of human cancers.

Original languageEnglish
Pages (from-to)4330-4340
Number of pages11
JournalCell Cycle
Volume10
Issue number24
DOIs
Publication statusPublished - Dec 15 2011

Fingerprint

Phosphotransferases
Mutant Proteins
Neoplasms
Growth
Small Interfering RNA
DNA Damage
Proteins
Maintenance
Cell Proliferation
Phenotype
Genes

Keywords

  • DNA damage
  • Feed back loop
  • Gain of function
  • Mutant p53
  • Polo-like kinase 2

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Valenti, F., Fausti, F., Biagioni, F., Shay, T., Fontemaggi, G., Domany, E., ... Di Agostino, S. (2011). Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop. Cell Cycle, 10(24), 4330-4340. https://doi.org/10.4161/cc.10.24.18682

Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop. / Valenti, Fabio; Fausti, Francesca; Biagioni, Francesca; Shay, Tal; Fontemaggi, Giulia; Domany, Eytan; Yaffe, Michael B.; Strano, Sabrina; Blandino, Giovanni; Di Agostino, Silvia.

In: Cell Cycle, Vol. 10, No. 24, 15.12.2011, p. 4330-4340.

Research output: Contribution to journalArticle

Valenti, F, Fausti, F, Biagioni, F, Shay, T, Fontemaggi, G, Domany, E, Yaffe, MB, Strano, S, Blandino, G & Di Agostino, S 2011, 'Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop', Cell Cycle, vol. 10, no. 24, pp. 4330-4340. https://doi.org/10.4161/cc.10.24.18682
Valenti F, Fausti F, Biagioni F, Shay T, Fontemaggi G, Domany E et al. Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop. Cell Cycle. 2011 Dec 15;10(24):4330-4340. https://doi.org/10.4161/cc.10.24.18682
Valenti, Fabio ; Fausti, Francesca ; Biagioni, Francesca ; Shay, Tal ; Fontemaggi, Giulia ; Domany, Eytan ; Yaffe, Michael B. ; Strano, Sabrina ; Blandino, Giovanni ; Di Agostino, Silvia. / Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop. In: Cell Cycle. 2011 ; Vol. 10, No. 24. pp. 4330-4340.
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