IRAS is an anti-apoptotic protein

Ann N Y Acad Sci. 2003 Dec;1009:400-12. doi: 10.1196/annals.1304.054.

Abstract

Active cell death, also known as apoptosis, has been implicated in the pathophysiology of diseases such as cancer, heart failure and neurodegenerative disorders. We report the anti-apoptotic function of IRAS, which was previously shown to bind imidazoline ligands. The amino acid sequence of human IRAS (hIRAS) is unrelated to known proteins, except for rat IRAS and a mouse homologue named nischarin, which binds the alpha5 integrin subunit of the fibronectin receptor. When stably transfected into PC12 cells, hIRAS localizes to the cytosol as a 167 kDa immunoreactive protein. Clonal PC12 cell lines expressing hIRAS displayed normal serum growth responses. However, hIRAS expression led to prolonged cell survival against known apoptotic stimuli: serum starvation or thapsigargin or staurosporine treatments. The apoptotic population of hIRAS-expressing cells was significantly reduced, and this protection was achieved by a decrease in caspase-3 activity, phosphatidylserine translocation, and nuclear fragmentation. Similar protective effect was obtained in COS7 cells transiently transfected with hIRAS. A partial activation of the PI3 kinase pathway is possibly implicated in the anti-apoptotic effect of IRAS. Thus, IRAS appears to represent a previously unknown anti-apoptotic protein involved in the regulation of cell survival.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • COS Cells
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Caspase 3
  • Caspases / metabolism
  • Cell Division / physiology
  • Cell Nucleus / metabolism
  • Chromones / metabolism
  • Culture Media, Serum-Free
  • Enzyme Inhibitors / metabolism
  • Humans
  • Imidazoline Receptors
  • Integrin alpha5beta1 / metabolism
  • Intracellular Signaling Peptides and Proteins*
  • Mice
  • Morpholines / metabolism
  • PC12 Cells
  • Rats
  • Receptor, Insulin / metabolism
  • Receptors, Drug / metabolism
  • Signal Transduction / physiology
  • Staurosporine / metabolism

Substances

  • Carrier Proteins
  • Chromones
  • Culture Media, Serum-Free
  • Enzyme Inhibitors
  • Imidazoline Receptors
  • Integrin alpha5beta1
  • Intracellular Signaling Peptides and Proteins
  • Morpholines
  • NISCH protein, human
  • Receptors, Drug
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Receptor, Insulin
  • CASP3 protein, human
  • Casp3 protein, mouse
  • Casp3 protein, rat
  • Caspase 3
  • Caspases
  • Staurosporine