Naslov
The role of the L5/L11-Mdm2-p53 signaling pathway in response to ribosomal and genotoxic stresses

Autori
Oršolić, Ines ; Jurada, Deana ; Volarević, Siniša

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

Izvornik
FEBS3+ Meeting and 11th Meeting of the Slovenian Biochemical Society - Book of Abstracts / Kos, Janko ; Poklar Ulrih, Nataša - Ljubljana : Slovenian Biochemical Society, 2015, 191-191

ISBN
978-961-93879-0-0

Skup
FEBS3+ Meeting "Molecules of Life" and 11th Meeting of the Slovenian Biochemical Society

Mjesto i datum
Portorož, Slovenija, 16.09.2015. - 19.09.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
ribosomal proteins; RPL5; RPL11; p53; DNA damage

Sažetak
The exposure of cells to various DNA-damaging stressors activates p53 to preserve cellular and genetic stability, preventing tumor development in mice and humans. The critical role of p53 in tumor suppression is supported by the observation that approximately 50% of all human cancers have mutations within this gene. Although it was largely accepted that common to all p53-activating stresses is DNA damage, research over the last decade has shown that disruption of ribosome biogenesis promotes binding of several distinct ribosomal proteins (RP) to Mdm2 resulting in inhibition of its E3 ubiquitin ligase activity towards p53. As a result, p53 accumulates within the cell and transcriptionally activates genes that regulate apoptosis, cell cycle checkpoints, metabolism and senescence. We have recently shown that ribosomal proteins (RP) L5 and L11 play a major role in p53 activation upon ribosomal biogenesis as well as DNA damaging stresses. Given the importance of RPL5 and RPL11 in p53 activation, we initiated a project to understand their role in the development of malignant tumors. Our efforts led to the identification of the first somatic cancer-associated missense mutations in the RPL5 and RPL11 genes in humans. Our current research focuses on understanding the molecular mechanisms by which RPL5 and RPL11 participate in p53 activation in response to ribosomal or genotoxic stress as well as providing insights into the functional significance of these cancer-associated mutations in RPL5 and RPL11 genes in p53 regulation and tumorigenesis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA