Our general area of interest We have been studying consequences of RP deficiencies in mammals for several years. Initially, 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 biogenesis. 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 (Fig. 2). Our main goals for the future are to understand the molecular basis of this checkpoint response and determine its role in pathogenesis of various diseases.
Fig. 2. The response of mammalian cells to a RP-deficiency. (A) Normal expression levels of RPS are required for physiological responses, such as cell growth, cell division and differentiation. (B) Reduced dosage of some RP genes could lead to the activation of p53. p53 can influence the fate of a RP-deficient cells via regulation of various biological responses. The outcome of p53 activation can be either adaptation of cells to a RP deficiency or various pathological manifestations.