( When cells get stressed their proteins...)Unfolded Proteins May Protect Cells from Dying,Health

When cells get stressed, their proteins go unfolded. It's a reaction with a straightforward name: the unfolded protein response. //

Now, new research from Rockefeller University shows that this phenomenon actually serves a protective role; rather than a sign that the cell has given up, it may be a mechanism by which the cells cope with adversity.

Diabetes, cancer, and neurodegenerative diseases including Huntington's and Parkinson's are linked to unfolded proteins. But Hermann Steller, head of the Strang Laboratory of Apoptosis and Cancer Biology at Rockefeller and a Howard Hughes Medical Institute investigator, focused on autosomal dominant retinitis pigmentosa (ADRP), which causes blindness. Unfolded proteins linked to ADRP accumulate in the endoplasmic reticulum, an organelle where proteins are manufactured and packaged for transport to the cell surface, unlike some other forms of the unfolded protein response that occur in the cell's cytoplasm.

To understand what impact the unfolded protein response had on the cell, Hyung Don Ryoo, a former postdoc in the Steller lab, used a protein called xbp1, whose mRNA is alternatively spliced when the cell is stressed and the unfolded protein response is activated. Ryoo rigged xbp1 with a fluorescent marker that would light up whenever this alternatively spliced version of xbp1 was made, allowing him to detect every time the cell initiated an unfolded protein response.

'Our work shows that the unfolded protein response is a protective pathway, and therapeutically this is the type of pathway you want to boost to protect cells from stress induced death,' says Steller, who is the Strang Professor at Rockefeller.

What's more, the researchers found that only cells that had endoplasmic reticulum stress, not cytoplasmic stress, made the fluorescently tagged xbp1 protein.

'Many researchers had bunched the stress response of the cytoplasmic and endoplasmic
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