Connecting the nucleolus to the cell cycle and human disease

FASEB J. 2014 Aug;28(8):3290-6. doi: 10.1096/fj.14-254680. Epub 2014 Apr 30.

Abstract

Long known as the center of ribosome synthesis, the nucleolus is connected to cell cycle regulation in more subtle ways. One is a surveillance system that reacts promptly when rRNA synthesis or processing is impaired, halting cell cycle progression. Conversely, the nucleolus also acts as a first-responder to growth-related stress signals. Here we review emerging concepts on how these "infraribosomal" links between the nucleolus and cell cycle progression operate in both forward and reverse gears. We offer perspectives on how new cancer therapeutic designs that target this infraribosomal mode of cell growth control may shape future clinical progress.

Keywords: cancer; cell cycle; ribosome synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Cycle / physiology*
  • Cell Nucleolus / physiology*
  • DNA Repair
  • Forecasting
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / metabolism
  • Humans
  • Models, Biological*
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Nuclear Proteins / physiology
  • Pol1 Transcription Initiation Complex Proteins / physiology
  • RNA, Ribosomal / biosynthesis
  • Ribosomal Proteins / deficiency
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / physiology
  • Ribosomes / metabolism*
  • Signal Transduction / physiology

Substances

  • Antineoplastic Agents
  • Nuclear Proteins
  • Pol1 Transcription Initiation Complex Proteins
  • RNA, Ribosomal
  • Ribosomal Proteins