Naslov
DNp73 stabilizes TAp73 protein

Autori
Slade, Neda ; Zaika, Alex ; Moll, Ute M.

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

Izvornik
19th Annual Meeting on Oncogenes / - , 2003

Skup
19th Annual Meeting on Oncogenes

Mjesto i datum
Frederick (MD), Sjedinjene Američke Države, 18.06.2003. - 21.06.2003

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
deltaNp73; stabilization; TAp73

Sažetak
The TP53 family member TP73 generates transactivating forms (TAp73) as well as a number of N-terminally truncated, transactivation-deficient transdominant isoforms. There are three such isoforms called DNp73, Ex2p73 and Ex2/3p73. Importantly, DNp73, which can be derived either from the TA promoter or an alternative promoter in Intron 3, is frequently overexpressed both on the RNA and protein level in a variety of human tumors. Using pulse chase experiments we systematically determined the half-lives of these N-terminally truncated forms. Although it is well established that DNp73 is a potent functional transdominant inhibitor of both wild type p53 and TAp73, we found that transfection of increasing amounts of DNp73 into H1299 and U2OS cells leads to a concomitant increase of exogenous and endogenous TAp73 protein. In contrast to TAp73, wild type p53 protein levels remain constant and are independent of the amount of DNp73 transfected. The accumulation of endogenous TAp73 was confirmed in both tet-on HeLa and tet-off SaOs2 cells expressing DNp73 from a doxycyclin-inducible promoter. Previously we showed that in tumors and cell lines DNp73 forms a complex with TAp73. Thus, it is likely that the stabilization of TAp73  by DNp73 is due to the formation of mixed oligomers with TAp73, thereby stabilizing TAp73 in an inactive form. This suggests a second, posttranslational mechanism synergistic to the frequently observed co-upregulation of TAp73 and DNp73 transcripts in human cancer. Future protein-based studies are needed to verify this relationship between TAp73 and DNp73 in primary tumors.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA