Disease Mechanisms - Miscellaneous
Part 3

The Heat-Shock Response

Steps towards the Heat Shock Response

When the cell recognizes that there are a lot of misfolded proteins, it triggers the heat-shock response. The first step is the activation of a transcription factor named heat-shock factor. The heat-shock factor can be activated very quickly once stress is recognized, which allows it to be a very effective protective mechanism.

In humans, there are actually three different heat-shock factors that trigger the heat-shock response. Having different forms of heat-shock factors allows the cell to have specialized heat-shock responses, depending on which kind of stress it is exposed to. All three of these heat-shock factors are very important, but for the purpose of this discussion, we will be referring to heat-shock factor 1. This factor is the main one involved in the stress response in HD.

Heat-shock factor 1 is activated in response to environmental and disease-related stress. During non-stressed conditions, heat-shock factor 1 is normally present in the cell as a monomer, or a single copy. This is its inactive, non-functional form. When the cell triggers the heat-shock response, three heat-shock factor 1 proteins bind together to form a trimer - the active form (See Figure 1).

This activated heat-shock factor 1 binds to DNA at regions where genes for heat-shock proteins are located. At this point, the number of heat-shock proteins produced in the cell dramatically increases. We will now look at how a few of these heat-shock protein families function when the cell is stressed, using HD as a model.

Last Modified: 04/12/2007

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