Naslov
The Role of Ribosomal Proteins L5 and L11 in Tumor Suppression

Autori
Oršolić, Ines ; Bursać, Slađana ; Volarević, Siniša

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
Functional Genomics Workshop

Mjesto i datum
Ljubljana, Slovenija, 15.10.2014. - 16.10.2014

Vrsta sudjelovanja
Ostalo

Vrsta recenzije
Nije recenziran

Ključne riječi
RPL5; RPL11; p53; ribosome biogenesis stress

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, but not other suggested "p53-activating" RPs, play a major role in p53 activation upon ribosome biogenesis stress. 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, suggesting that they play a role in malignant transformation. Our current research focuses on the characterization of functional significance of these newly identified mutations in the RPL5 and RPL11 genes in p53 regulation and tumorigenesis.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA