Ribosomal proteins and human diseases: pathogenesis, molecular mechanisms, and therapeutic implications

Med Res Rev. 2015 Mar;35(2):225-85. doi: 10.1002/med.21327. Epub 2014 Aug 28.


Ribosomes are essential components of the protein synthesis machinery. The process of ribosome biogenesis is well organized and tightly regulated. Recent studies have shown that ribosomal proteins (RPs) have extraribosomal functions that are involved in cell proliferation, differentiation, apoptosis, DNA repair, and other cellular processes. The dysfunction of RPs has been linked to the development and progression of hematological, metabolic, and cardiovascular diseases and cancer. Perturbation of ribosome biogenesis results in ribosomal stress, which triggers activation of the p53 signaling pathway through RPs-MDM2 interactions, resulting in p53-dependent cell cycle arrest and apoptosis. RPs also regulate cellular functions through p53-independent mechanisms. We herein review the recent advances in several forefronts of RP research, including the understanding of their biological features and roles in regulating cellular functions, maintaining cell homeostasis, and their involvement in the pathogenesis of human diseases. We also highlight the translational potential of this research for the identification of molecular biomarkers, and in the discovery and development of novel treatments for human diseases.

Keywords: RP-MDM2-p53 pathway; cancer; drug discovery; ribosomal protein; ribosomopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Nucleolus / metabolism
  • Disease*
  • Humans
  • Mitochondria / metabolism
  • Ribosomal Proteins / metabolism*
  • Ribosomes / metabolism
  • Stress, Physiological


  • Ribosomal Proteins