Naslov
Mutant p53 proteins inhibit transcriptional activity, but stabilize TAp73 due to hetereooligomer formation

Autori
Zorić, Arijana ; Ružđak, Matija ; Horvat, Anđela ; Slade, Neda

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
5th Mutant p53 Workshop / - Rim, 2011, 126-126

Skup
5th Mutant p53 Workshop

Mjesto i datum
Rim, Italija; Ariccia, Italija, 22.05.2011. - 25.05.2011

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
mutant p53; TAp73; dominant-negative; stabilization

Sažetak
After recent discovering of p63 and p73, the p53 family members, it became evident that to understand the p53 pathways, all of them have to be taken into account. p73 was shown to activate many p53 target genes, it is able to induce cell cycle arrest and apoptosis and is activated upon DNA damage. N-terminally truncated forms (ΔNp73) can act as potential transdominant inhibitors of both TAp73 (transactivation competent form) and wild type p53. On the other hand, mutant p53 proteins, most of which have lost tumor suppressor activity and gained oncogenic potential, are dominant negative inhibitors of TAp73. The mechanism of transdominant inhibitory activity can be explained through physical interaction. To determine the effect of tumor-derived p53 mutants (R175H, R248W, L194F, R249S, R280K, R282W) on p73 transcriptional activity, we performed reporter assay. The results have shown that all mutant inhibit transcriptional activity but with different efficiency. Furthermore, we have shown that p53 R248W and R280K mutants are the most efficient inhibitors of TAp73β apoptotic activity. Inhibitory interactions of two proteins often lead to stabilization of their components. We tested whether mutant p53 proteins can also induce stabilization and concomitant inactivation of p73 proteins. Our results have shown that all mutant p53 stabilize TAp73β with similar effect. Defining the interactions between p53/p73 would gain insight into how the p53 modulate the functions of p73. The discovery of p53/p73 network could have a major clinical impact in prognostic use and p53 targeted drug design.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA