Pregled bibliografske jedinice broj: 206258
Delta N p73, a dominant negative inhibitor of wild type p53 and TA p73, is upregulated in human tumors
Delta N p73, a dominant negative inhibitor of wild type p53 and TA p73, is upregulated in human tumors // 11th International p53 Workshop
Barcelona, Španjolska, 2002. (poster, međunarodna recenzija, sažetak, znanstveni)
CROSBI ID: 206258 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Delta N p73, a dominant negative inhibitor of wild type p53 and TA p73, is upregulated in human tumors
Autori
Zaika, Alex I. ; Slade, Neda ; Erster, Susan ; Sansome, Christine ; Joseph, Troy W. ; Pearl, Michael ; Chalas, Eva ; Moll, Ute M.
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
11th International p53 Workshop
/ - , 2002
Skup
11th International p53 Workshop
Mjesto i datum
Barcelona, Španjolska, 15.05.2002. - 19.05.2002
Vrsta sudjelovanja
Poster
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
p73; delta Np73; Ex2Del p73; apoptosis; deregulation in tumors
Sažetak
P73 has significant homology to p53. However, tumor-associated up-regulation of p73 and genetic data from human tumors and p73-deficient mice exclude a classical Knudson-type tumor suppressor role. We report that the human TP73 gene generates an NH2 terminally truncated isoform. DeltaNp73 derives from an alternative promoter in intron 3 and lacks the transactivation domain of full-length TAp73.Delta Np73 is frequently overexpressed in a variety of human cancers, but not in normal tissues. Delta Np73 acts as a potent transdominant inhibitor of wild-type p53 and transactivation-competent TAp73. DeltaNp73 efficiently counteracts transactivation function, apoptosis, and growth suppression mediated by wild-type p53 and TAp73, and confers drug resistance to wild-type p53 harboring tumor cells. Conversely, down-regulation of endogenous deltaNp73 levels by antisense methods alleviates its suppressive action and enhances p53- and TAp73-mediated apoptosis. DeltaNp73 is complexed with wild-type p53, as demonstrated by coimmunoprecipitation from cultured cells and primary tumors. Thus, deltaNp73 mediates a novel inactivation mechanism of p53 and TAp73 via a dominant-negative family network. Deregulated expression of deltaNp73 can bestow oncogenic activity upon the TP73 gene by functionally inactivating the suppressor action of p53 and TAp73. This trait might be selected for in human cancers.
Izvorni jezik
Engleski
Znanstvena područja
Biologija, Temeljne medicinske znanosti
POVEZANOST RADA
