Handling stress: life and death decisions at the cellular level

The daily life of a cell can be inordinately stressful. Two papers in the September 15th issue of Genes & Development highlight recent discoveries that have been made regarding how cells handle environmental stress, and decide whether or not their life is worth living. Both papers lend valuable insight into the ways that different cells respond to oxygen deprivation, or hypoxia.

Teetering on the Edge

A team of scientists led by Dr. Bohdan Wasylyk at the INSERM research center in France has discovered that the steroid receptor, GR, and the tumor suppressor, p53, interact during periods of oxygen deprivation to help balance the decision between cell survival and cell death.

p53 is commonly referred to as "the guardian of the genome" for its integral role in mediating either cell cycle arrest or cell death in response to various types of cell stress. Loss of p53 function can lead to unregulated cell proliferation, an event that is associated with the development of most tumors. The glucocorticoid receptor, GR, binds steroid hormones and helps to mediate the normal response to stress.

Dr. Wasylyk and colleagues determined that under hypoxic conditions p53 and ligand-bound GR directly associate with one another in the cytoplasm of the cell. This p53/GR complex is then bound by another protein, Hdm2, which facilitates the degredation of both p53 and GR. In this manner, the p53-mediated death response is held in check by GR, and the GR-mediated survival response is held in check by p53. This antagonistic interaction between p53 and GR represents a novel mechanism to balance cell survival and cell death in response to environmental stress.

Nervous Stress

Scientists from UMASS Medical School and Yale University School of Medicine report on the involvement of a key player in the stress response pathway in neurons. The JIP1 protein is a component of a pathway that is activated in response to ce

Contact: Nora Poppito
Cold Spring Harbor Laboratory

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