Ribosomal Proteins Control or Bypass p53 during Nucleolar Stress.

Annapina Russo,Giulia Russo

doi:10.3390/ijms18010140

Annapina Russo, Giulia Russo

Open Access

https://doi.org/10.3390/ijms18010140

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Abstract

The nucleolus is the site of ribosome biogenesis, a complex process that requires the coordinate activity of all three RNA polymerases and hundreds of non-ribosomal factors that participate in the maturation of ribosomal RNA (rRNA) and assembly of small and large subunits. Nevertheless, emerging studies have highlighted the fundamental role of the nucleolus in sensing a variety of cellular stress stimuli that target ribosome biogenesis. This condition is known as nucleolar stress and triggers several response pathways to maintain cell homeostasis, either p53-dependent or p53-independent. The mouse double minute (MDM2)-p53 stress signaling pathways are activated by multiple signals and are among the most important regulators of cellular homeostasis. In this review, we will focus on the role of ribosomal proteins in p53-dependent and p53-independent response to nucleolar stress considering novel identified regulators of these pathways. We describe, in particular, the role of ribosomal protein uL3 (rpL3) in p53-independent nucleolar stress signaling pathways.

Highlights

The nucleolus is a sub-nuclear compartment without membrane located within the cellular nucleus
The nucleolus is the site of ribosome biogenesis, a complex process that requires the coordination of several events leading to nuclear export of the mature 40S and 60S subunits to the cytoplasm (Figure 1)
This process requires the presence of hundreds of accessory or assembly factors represented by non-r-proteins and small nucleolar RNAs [3] and is generally coordinated with cell growth and sensitive to several cellular stimuli (Figure 1)

Summary

Introduction

The nucleolus is a sub-nuclear compartment without membrane located within the cellular nucleus. Ribosome-free rpL11 interacts with MDM2 promoting E2F-1 degradation; ribosome-free rpS14, rpL5 and rpL11 bind to 3 -UTR of c-Myc mRNA to enhance the recruitment of miRNA-induced silencing complex (miRISC) for c-Myc degradation; rpS14 and rpL11 negatively regulate c-Myc transcription activity. They bind to c-Myc box II domain and inhibit the recruitment of c-Myc co-activator TRRAP to c-Myc target gene promoters suppressing cell proliferation. Downregulation of E2F-1 expression is associated with the inhibition of cell proliferation [57]

Other p53-Independent Response Pathways to Nucleolar Stress

Wnt Target Peter Pan-NPM-BAX

Findings

Remarks and Perspectives