title: Mutant p53 oncogenic functions are sustained by Plk2 kinase through an autoregulatory feedback loop.
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 auto-regulatory 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 chemo-resistance, respectively. In turn, the siRNA-mediated knock down 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.
authors: Translational Oncogenomics Unit, Regina Elena Cancer Institute, Rome, Italy.
authors: Fabio
authors: F
authors: Valenti
authors: Francesca
authors: F
authors: Fausti
authors: Francesca
authors: F
authors: Biagioni
authors: Tal
authors: T
authors: Shay
authors: Giulia
authors: G
authors: Fontemaggi
authors: Eytan
authors: E
authors: Domany
authors: Michael B
authors: MB
authors: Yaffe
authors: Sabrina
authors: S
authors: Strano
authors: Giovanni
authors: G
authors: Blandino
authors: Silvia
authors: S
authors: Di Agostino
mesh_terms: D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004249:DNA Damage / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D050881:E1A-Associated p300 Protein / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D025461:Feedback, Physiological / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human; C496126:PLK2 protein, human; D017346:Protein Serine-Threonine Kinases