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Human securin interacts with p53 and modulates p53-mediated transcriptional activity and apoptosis

AuthorsBernal, Juan A.; Luna, Rosa ; Espina, Águeda G. ; Lázaro, Icíar; Ramos-Morales, Francisco; Romero, Francisco; Arias, Carmen ; Silva, Augusto ; Tortolero, María; Pintor-Toro, José Antonio
Issue Date2002
PublisherNature Publishing Group
CitationNature Genetics 32(2): 306-311 (2002)
AbstractThe gene PTTG1 (encoding the pituitary tumor-transforming 1 protein) is overexpressed in several different tumor types, is tumorigenic in vivo and shows transcriptional activity. The PTTG1 protein is cell-cycle regulated and was identified as the human securin (a category of proteins involved in the regulation of sister-chromatid separation) on the basis of biochemical similarities with the Pdslp protein of budding yeast and the Cut2p protein of fission yeast. To unravel the function of human securin in oncogenesis, we carried out a phage-display screening to identify proteins that inter-act with securin. Notably, we isolated the p53 tumor suppressor. Pull-down and coimmunoprecipitation assays demonstrated that p53 interacts specifically with securin both in vitro and in vivo. This interaction blocks the specific binding of p53 to DNA and inhibits its transcriptional activity. Securin also inhibits the ability of p53 to induce cell death. Moreover, we observed that transfection of H1299 cells with securin induced an accumulation of G2 cells that compensated for the loss of G2 cells caused by transfection with p53. We demonstrated the physiological relevance of this interaction in PTTG1-deficient human tumor cells (PTTG1-1-): both apoptotic and transactivating functions of p53 were potentiated in these cells compared to parental cells. We propose that the oncogenic effect of increased expression of securin may result from modulation of p53 functions.
Identifiersdoi: 10.1038/ng997
issn: 1061-4036
e-issn: 1546-1718
Appears in Collections:(IRNAS) Artículos
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