engleski

Regulation of the p53 tumor suppressor by ribosomal proteins

Nascent ribosome synthesis is required during cell growth, proliferation and differentiation. It is temporally and spatially organized within the nucleolus, where rRNAs are transcribed, processed, modified and assembled with ribosomal proteins (Rps) to generate the mature 40S and 60S ribosomal subunits. Rps participate in additional steps in ribosome synthesis in the nucleoplasm and the cytoplasm, such as transport of ribosomal precursors, stabilization of ribosome structure and regulation of different steps in protein synthesis. In addition to their conventional role in ribosome synthesis and mRNA translation, some Rps appear to possess extra-ribosomal functions. Deficiencies of Rps in mammals lead to sever pathological conditions but the relative contribution of the impaired protein synthesis and extra-ribosomal function to the phenotype is poorly understood. In a search for the mechanism(s) involved, we demonstrated that inducible deletion of the Rps6 gene in the liver of adult mice inhibits the synthesis of the 40S ribosomal subunit as well as proliferation of liver cells following partial hepatectomy, despite seemingly unaffected protein synthesis. These observations suggested the existence of a novel checkpoint, downstream of the deficiency in ribosome synthesis. Most recently, our in vivo studies provided convincing evidence for the existence of this checkpoint and demonstrated that the p53 tumor suppressor is its critical component. I will discuss our current efforts to understand the molecular basis of this checkpoint response and its role in the pathogenesis of various diseases.

p53 tumour suppressor

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