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Handeling Stress: Life And Death Decisions At The Cellular Level

Date:
September 17, 2001
Source:
Cold Spring Harbor Laboratory
Summary:
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.
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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 cell stress and can trigger cell death. JIP1 binds to a control protein, JNK, that regulates the activity of other proteins through the addition of phosphate groups. It is thought that JIP1 acts as a scaffold protein that facilitates the assembly of specific signaling complexes.

Dr. Davis and colleagues now show that in response to severe hypoxic stress, JIP1 in neurons is relocated from the neurites to the cell body where it forms a complex with activated JNK. But is JIP1 really required for JNK activation in response to stress? To address this question, the team generated a strain of mice deficient in JIP1. While JIP1-deficient mice were viable and fertile, studies on these mice showed that their neurons did not respond to stress. When JIP1-deficient neurons were exposed to hypoxic stress, JNK was not activated and stress-induced apoptosis was therefore reduced. Thus, JIP1 is clearly required for JNK activation and is a critical component of the stress-induced JNK signaling cascade.

The JNK stress pathway is thought to be important in many pathological conditions including the progression of some neurodegenerative diseases such as Huntington’s and also in cancer. This pathway therefore offers potential targets for therapeutic intervention. The identification of critical components of this signaling pathway, such as JIP1, offers new routes to understand how this pathway is regulated and potential ways of manipulating it to combat disease.


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The above post is reprinted from materials provided by Cold Spring Harbor Laboratory. Note: Materials may be edited for content and length.


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Cold Spring Harbor Laboratory. "Handeling Stress: Life And Death Decisions At The Cellular Level." ScienceDaily. ScienceDaily, 17 September 2001. <www.sciencedaily.com/releases/2001/09/010917075255.htm>.
Cold Spring Harbor Laboratory. (2001, September 17). Handeling Stress: Life And Death Decisions At The Cellular Level. ScienceDaily. Retrieved August 4, 2015 from www.sciencedaily.com/releases/2001/09/010917075255.htm
Cold Spring Harbor Laboratory. "Handeling Stress: Life And Death Decisions At The Cellular Level." ScienceDaily. www.sciencedaily.com/releases/2001/09/010917075255.htm (accessed August 4, 2015).

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