Naslov
Regulation of p53 by Ribosomal Stress

Autori
Volarević, Siniša

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

Skup
Advances in Immunology and Cancer Biology

Mjesto i datum
Istanbul, Turska, 15.04.2011. - 17.04.2011

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
p53; ribosomal stress

Sažetak
The capacity of p53 protein to detect many cancer-related stresses and appropriately respond by regulating target genes that induce various biological responses is essential for prevention of malignancies in humans. Currently, it is not known how such diversity of stress signals can be integrated by a single molecule. A few years ago we reported an observation that genetic disruption of ribosome biogenesis by conditional deletion of one allele of ribosomal protein S6 gene elicits a p53-dependent checkpoint response. Based on the available literature other researchers proposed that most p53-inducing stresses compromise ribosome biogenesis and nucleolar structure. Furthermore, RPL5, RPL11, RPL23, RPL26 and RPS7 have been suggested as transducers of p53-activating signals in response to pharmacologic inhibition of ribosome biogenesis. We have recently shown that a number ribosomal and non-ribosomal cellular stresses utilize RPL5, RPL11 but not RPL23, RPL26 and RPS7 to activate the p53 tumor suppressor. 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 human colon cancers, granting an advantage to cells in escaping p53 tumor suppression. By genomic sequencing of DNA from colon cancer samples we identified a few cancer-associated heterozygous mutations in the coding regions of RPL11 and RPL5. We are planning to test the possibility that RPL5 and RPL11 are bona fide tumor suppressors in the near future

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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