How cell processes round up and dump damaged proteins
A very large protease called a proteasome** is responsible for degrading the vast majority of proteins in a cell; it may be made up of as many as 40 proteins.
UCH37 enzyme** is one of the regulatory enzymes that associates with the proteasome**.
What does ubiquitin protein do? The cells in your body build up and break down proteins at a rapid rate. Ubiquitin attaches to proteins, tagging them for disposal. Tagged proteins are taken to proteasomes** to be destroyed. Just before the protein enters the proteasome, ubiquitin is disconnected to be used again. src
Ubiquitin protein in addition to modifying other proteins, modifies itself resulting in a wide array of chains.. Some of these chains can have extensive branching. We found that UCH37** removes branch points from chains, allowing degradation to proceed.
Could eventually lead to a new cancer treatment because cancer cells need the proteasome to grow and proliferate.
Many cancer cells are essentially addicted to proteasome function, its cells produce proteins at such a fast rate that mistakes are made, and if these are not cleared out, cells can’t function. Since UCH37** aids in clearing out proteins, it could be a useful therapeutic target to add to the proteasome** inhibitors that have already been successful in the clinic.
We had to come up with a way to generate a wide variety of ubiquitin chains that would represent the potential diversity in a cell. Using that new library of ubiquitin chains allowed us to interrogate the activity of UCH37** in a controlled setting. That series of experiments gave us the first clue that this enzyme was doing something unique**.
It took us eight years to figure it out, and I’m very proud of this work. We had to develop a lot of new methods and tools to understand what this enzyme is doing.
study by Eric Strieter.
src - https://www.umass.edu/newsoffice/article/how-cell-processes-round-and-dump-damaged ref - https://www.eurekalert.org/pub_releases/2020-11/uoma-hcp110620.php
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