How Cell Processes Round Up and Dump Damaged Proteins
Arthur T Knackerbracket has found the following story:
In a new paper with results that senior author Eric Strieter at the University of Massachusetts Amherst calls "incredibly surprising," he and his chemistry lab group report that they have discovered how an enzyme known as UCH37 regulates a cell's waste management system.
[...] As he explains, 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. It has been known for more than 20 years that UCH37 is one of the regulatory enzymes that associates with the proteasome, he adds, "but no one understood what it was doing."
It turns out that the crux of the whole process, he adds, is how complicated modifications in a small protein called ubiquitin can be. "In addition to modifying other proteins, ubiquitin modifies itself resulting in a wide array of chains. Some of these chains can have extensive branching. We found that UCH37 removes branchpoints from chains, allowing degradation to proceed."
Writing this week in Molecular Cell, he and first author and Ph.D. candidate Kirandeep Deol, who led and conducted the experiments, with co-authors Sean Crowe, Jiale Du, Heather Bisbee and Robert Guenette, discuss how they answered the question. The work was supported by the NIH's National Institute of General Medical Sciences.
This advance could eventually lead to a new cancer treatment, Strieter says, because cancer cells need the proteasome to grow and proliferate. "Many cancer cells are essentially addicted to proteasome function," he points out. "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."
Journal Reference:
Kirandeep K.Deol, Sean O.Crowe, Jiale Du, Heather A.Bisbee, Robert G.Guenette, Eric R.Strieter, Proteasome-Bound UCH37/UCHL5 Debranches Ubiquitin Chains to Promote Degradation, Molecular Cell (DOI: 10.1016/j.molcel.2020.10.017)
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