IRAS Is an Anti-Apoptotic Protein

• Published in: Annals of the New York Academy of Sciences 2003-12, Vol.1009 (1), p.400-412
• Main Authors: DONTENWILL, MONIQUE, PILETZ, JOHN E., CHEN, MICHAEL, BALDWIN, JAMES, PASCAL, GÉRALDINE, RONDÉ, PHILIPPE, DUPUY, LAURENCE, GRENEY, HUGUES, TAKEDA, KEN, BOUSQUETD, PASCAL
• Format: Article
• Language: English
• Subjects: Animals; apoptosis; Apoptosis - physiology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Carrier Proteins - physiology; Caspase 3; Caspases - metabolism; Cell Division - physiology; Cell Nucleus - metabolism; Chromones - metabolism; COS Cells; Culture Media, Serum-Free; Enzyme Inhibitors - metabolism; Humans; Imidazoline Receptors; Integrin alpha5beta1 - metabolism; Intracellular Signaling Peptides and Proteins; IRAS; Mice; Morpholines - metabolism; nischarin; PC12 Cells; Rats; Receptor, Insulin - metabolism; Receptors, Drug - metabolism; Signal Transduction - physiology; Staurosporine - metabolism
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1196/annals.1304.054

: 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.