Editors' ChoiceCell proliferation

Integrating Stress and Growth Signals

STKE  14 Jun 2005:
Vol. 2005, Issue 288, pp. tw218
DOI: 10.1126/stke.2882005tw218

To effectively regulate cell growth and proliferation, cells need to interpret signals that serve to measure whether internal and external conditions are favorable--by sensing the presence of growth factors, nutrients, and cellular energy stores--along with signals generated in response to stresses that might prove disruptive to successful proliferation. Many of the latter activate signaling through the tumor suppressor protein p53, whereas growth regulatory pathways feed into activation of the phosphoinositide 3-kinase-related kinase TOR (target of rapamycin). Feng et al. describe experiments that demonstrate cross talk between these two signaling pathways that appears to provide a mechanism to integrate information from the two pathways. In mouse embryo fibroblasts, activation of p53 after stress induced by DNA damage inhibited TOR activity and its downstream effects, and such effects were lost in cells lacking p53. Pharmacological inhibition of AMPK (adenosine monophosphate-activated kinase), the protein kinase that regulates TOR in response to the nutritional status of the cell, indicated that AMPK also mediated the effect of p53 on TOR. Conversely, cells that were deprived of glucose showed phosphorylation of p53 that represents one step in the activation of that protein. The authors suggest that such signaling between nutrient or metabolic pathway and sensors of cellular stress may be necessary to ensure normal cell growth and proliferation.

Z. Feng, H. Zhang, A. J. Levine, S. Jin, The coordinate regulation of the p53 and mTOR pathways in cells. Proc. Natl. Acad. Sci. U.S.A. 102, 8204-8209 (2005). [Abstract] [Full Text]