Naslov
TAp73/deltaNp73 ratios and chemosensitivity

Autori
Slade, Neda ; Zorić, Arijana ; Moll, Ute M. ; Pavelić, Jasminka.

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

Izvornik
FEBS Special Meeting on Cellular Signaling-Dubrovnik 2006 / Đikić, Ivan ; Husnjak, Koraljka - Zagreb : Institut Ruđer Bošković, 2006, 254-255

ISBN
953-6690-59-4

Skup
FEBS Special Meeting on Cellular Signaling

Mjesto i datum
Dubrovnik, Hrvatska, 26.05.2006. - 01.06.2006

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
p73 isoforms; DNA damage

Sažetak
The p53 family member p73 generates transactivating forms (TAp73) as well as a number of N-terminally truncated, transactivation-deficient transdominant isoforms (collectively called ∆ TAp73). There are three such isoforms called ∆ Np73, Ex2p73 and Ex2/3p73. ∆ Np73, which can be derived either from the TA promoter (P1) or an alternative P2 promoter in intron 3, is frequently overexpressed both on the RNA and protein level in a variety of human tumors, and has a dominant negative effect on TAp73 and w.t. p53. TAp73 was shown to be activated by variety of DNA damaging agents that do induce p53 as well. Here we confirmed TAp73 upregulation upon cell stress. Using quantitative real time PCR we determined expression of all known p73 N-terminal transcripts (TAp73, ∆ Np73, ∆ N'p73, Ex2del p73 and Ex2/3del p73) in H1299 and RKO cells after treatment by several cytotoxic DNA damaging agents (cisplatin, doxorubicin, etoposide and camptothecin) or exposition to  -irradiation. Depending on the type of DNA damage, the most elevated isoforms were TAp73 and Ex2/3del p73. Oncogenic form  Np73 was only slightly elevated. We confirmed our results on protein level by western blot. We correlated p73 isoform expression profile with cell survival and found out that there is almost no cytotoxic effect in concentrations that cause upregulation of specific isoforms. Furthermore, to assess the contribution of ∆ p73 isoform to chemoresistance, we used Hela ∆ Np73 tet on inducible cell line with stably transfected ∆ Np73. After induction and subsequent treatment with several DNA damaging agents, we investigated the cell survival and ∆ Np73 protein expression. The results confirmed that, although dominant negative inhibitor of tumor suppressor genes p53 and p73, ∆ Np73 protein is elevated upon DNA damage. Interestingly, measuring cell viability, we found that ∆ Np73 expressing cells are more resistant to DNA damage. Probably TA/∆ Np73 ratios determine the p73 response to cytotoxic cellular stress.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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