In:
eLife, eLife Sciences Publications, Ltd, Vol. 3 ( 2014-09-16)
Abstract:
Living cells must be able to withstand changes in the environment. For example, if there is a sudden increase in temperature—which could damage proteins or other molecules—most cells can respond with the ‘heat shock response’. In humans and other mammals, a single protein called heat shock factor 1 triggers the production of numerous heat shock proteins that protect the cell from the detrimental effects of high temperatures. Most heat shock proteins protect cells by binding to, and stabilizing, other molecules in the cell; this prevents these molecules from being damaged or from aggregating and allows them to continue to function as normal. A protein called eEF1A1 is involved in the final stages of protein production and also enhances the function of heat shock factor 1 during the heat shock response. To make a protein, an enzyme called RNA polymerase transcribes DNA in the nucleus of the cell into a messenger RNA molecule that then exits the nucleus and binds to a ribosome. This molecular machine then translates the messenger RNA sequence into a protein by joining together individual building blocks called amino acids in the correct order. Like other elongation factors, eEF1A1 helps to select the amino acids that match the sequence of the messenger RNA template. However, it was unclear how eEF1A1 helped to protect cells during the heat shock response. Nudler et al. have now engineered cells—from humans and mice—that make less of the eEF1A1 protein than normal. These cells had enough of this protein to support their growth and development under normal conditions, but not enough to help during the heat shock response. When these cells are subjected to a sudden increase in temperature, they fail to produce a sufficient amount of major heat shock proteins. Heat shock factor 1 is needed to transcribe the genes that encode these heat shock proteins, and Nudler et al. found that eEF1A1 must bind to heat shock factor 1 and then to a moving RNA polymerase for these genes to be transcribed efficiently. Moreover, the eEF1A1 protein was shown to bind to and stabilize the heat shock proteins' messenger RNAs, and aid their export from the nucleus and their binding to the ribosome. These newly discovered roles for eEF1A1 during the heat shock response highlight this elongation factor as a promising drug target for treating diseases where protein folding goes awry, for example in Alzheimer's or Parkinson's disease. In adults, neurons do not make enough eEF1A1, and Nudler et al. suggest that enabling these cells to make more of this protein could help to treat a range of neurodegenerative conditions.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.03164.001
DOI:
10.7554/eLife.03164.002
DOI:
10.7554/eLife.03164.003
DOI:
10.7554/eLife.03164.004
DOI:
10.7554/eLife.03164.005
DOI:
10.7554/eLife.03164.006
DOI:
10.7554/eLife.03164.007
DOI:
10.7554/eLife.03164.008
DOI:
10.7554/eLife.03164.009
DOI:
10.7554/eLife.03164.010
DOI:
10.7554/eLife.03164.011
DOI:
10.7554/eLife.03164.012
DOI:
10.7554/eLife.03164.013
DOI:
10.7554/eLife.03164.014
DOI:
10.7554/eLife.03164.015
DOI:
10.7554/eLife.03164.016
DOI:
10.7554/eLife.03164.017
DOI:
10.7554/eLife.03164.018
DOI:
10.7554/eLife.03164.019
DOI:
10.7554/eLife.03164.020
DOI:
10.7554/eLife.03164.021
DOI:
10.7554/eLife.03164.022
DOI:
10.7554/eLife.03164.023
DOI:
10.7554/eLife.03164.024
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2014
detail.hit.zdb_id:
2687154-3
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