@article{7ab6838680894fe8a9ff20a7a0ef2078,
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 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.",
keywords = "DNA damage, Feed back loop, Gain of function, Mutant p53, Polo-like kinase 2",
author = "Fabio Valenti and Francesca Fausti and Francesca Biagioni and Tal Shay and Giulia Fontemaggi and Eytan Domany and Yaffe, {Michael B.} and Sabrina Strano and Giovanni Blandino and {Di Agostino}, Silvia",
note = "Funding Information: and 22. The analysis was performed by using a specific commer-We wish to thank Geraldine Williams and Tania Merlino for cial Plk2 FAMTM Probe (Applied Biosystems). Quantification of manuscript editing and Prof. Claudio Sette for help in immu-glyceraldehydes-3-phosphate dehydrogenase (GAPDH) mRNA nokinase assays. This work was supported by the Italian (as an internal control for gene expression in the cells) was per-Association for Cancer Research (AIRC) to S.S. and G.B., by formed using TaqMan{\textregistered} Human GAPDH Control Reagents Italian Association for Cancer Research (AIRC-MFAG n° 9046) (with VICTM Probe, Applied Biosystems). to S. Di A., by Lega Italiana Tumori to S.S., by Ministero della Chromatin immunoprecipitation assay. ChIP assay was per-Salute, by Alleanza contro il Cancro, Fondazione Veronesi and formed as described in references 21 and 22. The following anti-INAIL to G.B., and by European Community (EC) Active p53 bodies were used: 3 μl of sheep serum αp53 Ab7 (Calbiochem), (to G.B.) and Mutant p53 consortia (to G.B. and E.D.). E.D. is 5 μl of rabbit polyclonal αNF-YB (gift of R. Mantovani), 1 μg incumbent of the Henry J. Leir Professorial Chair. E.D. and T.S. of rabbit polyclonal αp300 (Santa Cruz), 6 μl of rabbit serum were supported also by a grant from the Ridgefield Foundation. αH4Acetylated (Upstate), 3 μl of rabbit polyclonal αPlk2 antibody This publication reflects the authors{\textquoteright} views and not necessarily (Calbiochem)· The primers sequences of the human promoters those of the European Community. used in the PCR reactions are: I CAAT box F5'-CTG CAC AGC AAA ATC TGG AA-3', R5'-CCT GGT TCC TGG AGA GTC Note AA-3'; II CAAT box F5'-CTT CGA CAC CTA ACG GCA TT-3', Supplemental material can be found at:",
year = "2011",
month = dec,
day = "15",
doi = "10.4161/cc.10.24.18682",
language = "English",
volume = "10",
pages = "4330--4340",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Taylor and Francis Ltd.",
number = "24",
}