Developmentally regulated GTPases: structure, function and roles in disease

Cell Mol Life Sci. 2021 Dec;78(23):7219-7235. doi: 10.1007/s00018-021-03961-0. Epub 2021 Oct 19.

Abstract

GTPases are a large superfamily of evolutionarily conserved proteins involved in a variety of fundamental cellular processes. The developmentally regulated GTP-binding protein (DRG) subfamily of GTPases consists of two highly conserved paralogs, DRG1 and DRG2, both of which have been implicated in the regulation of cell proliferation, translation and microtubules. Furthermore, DRG1 and 2 proteins both have a conserved binding partner, DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively, that prevents them from being degraded. Similar to DRGs, the DFRP proteins have also been studied in the context of cell growth control and translation. Despite these proteins having been implicated in several fundamental cellular processes they remain relatively poorly characterized, however. In this review, we provide an overview of the structural biology and biochemistry of DRG GTPases and discuss current understanding of DRGs and DFRPs in normal physiology, as well as their emerging roles in diseases such as cancer.

Keywords: GTPase; Gir2; Rbg1; Rbg2; Ribosome; Tma46; Translation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Proliferation / physiology*
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation / physiology*
  • Humans
  • Microtubules / metabolism
  • Neoplasms / pathology*
  • Protein Biosynthesis / physiology
  • Protein Domains / physiology
  • RNA-Binding Proteins / metabolism

Substances

  • DRG2 protein, human
  • RNA-Binding Proteins
  • ZC3H15 protein, human
  • developmentally regulated GTP-binding protein
  • GTP-Binding Proteins