Initiating cellular stress responses

Cell. 2004 Jul 9;118(1):9-17. doi: 10.1016/j.cell.2004.06.023.


The phosphoinositide 3-kinase related kinases (PIKKs) mediate responses to diverse stresses, including DNA double-strand breaks (DSBs), abnormal replication fork progression, the recognition of premature termination codons in mRNAs, and inadequate nutrient availability. Rigorous control of these kinases limits cellular damage and promotes cell viability in the presence of stress. Control mechanisms include the localization of PIKKs into multiprotein complexes at the sites of damage and mediation of protein-protein contacts such that substrates are allowed access to the PIKK catalytic domains.

Publication types

  • Review

MeSH terms

  • Animals
  • Catalytic Domain
  • Cell Survival
  • DNA Damage*
  • DNA Replication*
  • DNA-Binding Proteins
  • Enzyme Activation
  • Humans
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / chemistry
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Protein Structure, Tertiary
  • Stress, Physiological / genetics*
  • Substrate Specificity


  • DNA-Binding Proteins
  • Phosphatidylinositol 3-Kinases