Naslov
Ribosomal protein L5 and L11 play a major role in p53 activation upon ribosomal and genotoxic stresses

Autori
Cokarić, Brdovčak, Maja ; Bursać, Slađana ; Oršolić, Ines ; Jurada, Deana ; Volarević, Siniša

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

Izvornik
VI. Hrvatski kongres humane genetike - knjiga sažetaka / - , 2015

Skup
VI. HRVATSKI KONGRES HUMANE GENETIKE

Mjesto i datum
Split, Hrvatska, 05.11.2015. - 07.11.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
ribosome biogenesis; p53; cancer

Sažetak
The exposure of cells to various stressors activates the p53 tumor suppressor, a transcription factor that regulates many genes which induce various biological responses such as cell cycle arrest, apoptosis, senesence, metabolic changes and DNA repair. This activation is essential for prevention of malignancies in humans. Given the fact that loss of wild-type p53 provides many selective advantages to cells, it is not surprising that ~50% of all human cancers have mutations within the TP53 gene. Although DNA damage is common to most p53-activating stresses, evidence accumulated over the last decade suggests that perturbation of ribosome biogenesis triggers binding of several ribosomal proteins (RP) to Mdm2, which inhibits Mdm2's E3 ubiquitin ligase function toward p53 leading to p53 up- regulation independently of DNA damage. We have recently shown that ribosomal proteins RPL5 and RPL11 play a major role in p53 activation upon ribosomal biogenesis as well as DNA damaging stresses. Given the essential role of RPL5 and RPL11 in p53 activation after exposure of cells to various stressors, we hypothesized that mutations in these genes could arise in malignant tumors, granting an advantage to cells in escaping p53 tumor suppression. Consistent with the importance of RPL5 and RPL11 in p53 activation we identified the first somatic cancer-associated missense heterozygous mutations in the RPL5 and RPL11 genes in humans. In the future, we plan to elucidate molecular mechanisms of p53 activation by RPL5 and RPL11, after genotoxic and ribosomal stresses, and determine their role in the pathogenesis of malignant tumors.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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