Cell Biology

Talking About Stress

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Science  31 Oct 2008:
Vol. 322, Issue 5902, pp. 653
DOI: 10.1126/science.322.5902.653c

Cells encounter many different forms of stress and have evolved a variety of methods to deal with them. They tackle relatively minor stresses, such as excessive heat or insufficient oxygen (hypoxia), by forming cytoplasmic stress granules, which prevent the accumulation of defective proteins that can irreparably damage the cell. However, some stresses, including x-rays and DNA-damaging agents, are insurmountable, and the cell acknowledges defeat by killing itself in a process called apoptosis. This is triggered via the intracellular signaling cascades known as the stress-activated p38 and JNK MAPK (SAPK) pathways. Whether and how these two mechanisms of stress management are connected was unknown.

Arimoto et al. find that the formation of stress granules in response to minor stresses specifically inhibits the SAPK-mediated cell death response, indicating a connection between the two pathways. They found that the signaling scaffold protein RACK1 is required for the apoptotic response by binding directly to a protein in the SAPK pathway. However, during minor stresses RACK1 becomes sequestered within the cytoplasmic stress granules, thereby inhibiting apoptosis. The authors also showed that when cells are exposed to both types of stresses simultaneously, SAPK-mediated apoptosis is blocked. This mechanism of cross talk between two stress-management pathways could explain in part why cancer cells, which live under the constant minor stress of hypoxia, are resistant to apoptosis induced by radiotherapy and chemotherapy. — HP*

Nat. Cell Biol., 10.1038/ncb1791 (2008).

  • * Helen Pickersgill and Chris Surridge are locum editors in Science's editorial department.

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