Naslov
Death receptors and p53 dependent impairment of UV-induced apoptosis in FADD knockouts cells

Autori
Radnic, Maja ; Marijanovic, Inga ; Nagy, Biserka

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

Izvornik
European Journal of Cancer Supplements, Volume 6, Issue 9 / - : Elsevier, 2008

Skup
20th Meeting of the European Association for Cancer Research

Mjesto i datum
Lyon, Francuska, 05.06.2008. - 08.06.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
FADD; death receptors; apoptosis

Sažetak
Ultraviolet (UV) irradiation is the cause of many adverse biological effects including development of cancer and aging. UV light targets both membrane receptors and nuclear DNA, thus evoking signals triggering apoptosis. In UV mediated apoptosis different molecular pathways are involved including DNAdamage, activation of tumor suppressor gene p53, triggering of cell death receptors either directly or by autocrine release of death ligants, mitochondrial damage and cytochrome C release. Detailed knowledge about the interplay between these pathways will increase our understanding of photo-carcinogenesis. To investigate comparatively the role of death receptors apoptotic signaling pathway and participation of the p53 mutation in the signaling cascade of UV induced apoptosis we used mouse embryonic cell lines from knockout mice deficient for death-domain-containing adaptor molecules FADD (Fas-associated protein with death domain). FADD is responsible for downstream signal transduction of death receptors belonging to the tumor necrosis factor (TNF) superfamily. Survival, apoptosis, and p53 mutations studies revealed that exposure of two cell lines, knockout and wild type, to UV-C radiation and TNF. As expected, FADD knockout cells were protected completely from death induced by TNF. The results indicate that apoptosis induced by UV-C light does not require FADD protein. The knockout cells were more sensitive than wild-type cells with respect to cell death. Allele- specific PCR detection of p53 in genomic DNAfrom UV-C irradiated knockout and wild type cells were analyzed by gel electrophoresis. The results show that UV-C induced apoptosis is independent of functional p53 for which the FADD knockout cells showed to be mutated. We challenge the hypothesis that UV carcinogenesis in wild type cells includes a loss of FADD function and generation of p53 mutations.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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