Internal ribosome initiation of translation and the control of cell death.
The majority of cellular stresses lead to the inhibition of cap-dependent translation. Some mRNAs, however, are translated by a cap-independent mechanism, mediated by ribosome binding to internal ribosome entry site (IRES) elements located in the 5' untranslated region. Interestingly, IRES elements are found in the mRNAs of several survival factors, oncogenes and proteins crucially involved in the control of apoptosis. These mRNAs are translated under a variety of stress conditions, including hypoxia, serum deprivation, irradiation and apoptosis. Thus, IRES-mediated translational control might have evolved to regulate cellular responses in acute but transient stress conditions that would otherwise lead to cell death.
Holcik
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M
Solange Gauthier Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, ON, K1H 8L1, Ottawa, Canada. martin@mgcheo.med.uottawa.ca
Sonenberg
N
N
Korneluk
R G
RG
D020121:5' Untranslated Regions; D017209:Apoptosis / Q000502:physiology*; D015687:Cell Hypoxia; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D005720:Gamma Rays; D046911:Macromolecular Substances; D008957:Models, Genetic; D010445:Peptide Elongation Factors / Q000502:physiology; D010448:Peptide Initiation Factors / Q000502:physiology; D010849:Picornaviridae / Q000235:genetics; D014176:Protein Biosynthesis / Q000528:radiation effects; D020033:Protein Isoforms / Q000502:physiology; D012315:RNA Caps / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid; D012270:Ribosomes / Q000502:physiology*
D020121:5' Untranslated Regions; D016895:Culture Media, Serum-Free; D046911:Macromolecular Substances; D010445:Peptide Elongation Factors; D010448:Peptide Initiation Factors; D020033:Protein Isoforms; D012315:RNA Caps; D012333:RNA, Messenger; D012367:RNA, Viral