Naslov
Activation of the tumor suppressor p53 upon impairment of ribosome biogenesis

Autori
Bursać, Slađana ; Cokarić Brdovčak, Maja ; Donati, Giulio ; Volarević, Siniša

Izvornik
Biochimica et biophysica acta-molecular basis of disease (0925-4439) 1842 (2013), 6; 817-830

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, pregledni rad, stručni

Ključne riječi
ribosome biogenesis stress; p53; RPL5; RPL11; 5S rRNA; Ribosomopathies

Sažetak
Errors in ribosome biogenesis can result in quantitative or qualitative defects in protein synthesis and consequently lead to improper execution of the genetic program and the development of specific diseases. Evidence has accumulated over the last decade suggesting that perturbation of ribosome biogenesis triggers a p53-activating checkpoint signaling pathway, often referred to as the ribosome biogenesis stress checkpoint pathway. Although it was originally suggested that p53 has a prominent role in preventing diseases by monitoring the fidelity of ribosome biogenesis, recent work has demonstrated that p53 activation upon impairment of ribosome biogenesis also mediates pathological manifestations in humans. Perturbations of ribosome biogenesis can trigger a p53-dependent checkpoint signaling pathway independent of DNA damage and the tumor suppressor ARF through inhibitory interactions of specific ribosomal components with the p53 negative regulator, Mdm2. Here we review the recent advances made toward understanding of this newly-recognized checkpoint signaling pathway, its role in health and disease, and discuss possible future directions in this exciting research field.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA