Protein Degradation

An article in Science Daily describes that proteins do not last forever; they deteriorate and are degraded in the cell back into amino acids and then recycled into new proteins.  Proteasome, the cell’s protein recycler, gets rid of the unwanted toxic protein.  This new discovery can help with treating muscle waste, neurodegeneration and cancer.  New evidence shows that the proteasome is regulated, getting ready for activity when the cell has a large protein turnover.  Researchers have found an enzyme tankyrase that regulates the proteasome’s activity.  Researchers also found a molecule, XAV939 that inhibits tankyrase and blocks the activity of proteasome.

Tankyrase was identified for its role in elongating telomeres, the ends of a chromosome.  Researchers discovered, through a series of experiments in fly and human cells, that tankyrase completes a process called ADP-ribosylation to modify PI31.  This process regulates the activity and assembly of proteasome subunits into the active complex, 26S.

Proteasome is currently being developed for cancer therapies. The FDA has approved Valcade, a proteasome inhibitor being used for the treatment of multiple myeloma and mantle cell lymphoma. But you can be resistant to Valcade, or have symptoms of peripheral neuropathy.  For multiple myeloma proteasome activity needs to increase.

The researchers also have also linked proteasome regulation and metabolism, which suggest that the proteasome digests too much protein.  This can lead to muscle loss.

Stefan Maas, at the National Institute of Health’s National Institute of General Medical Sciences, explains that “this discovery reveals fundamental insights into protein degradation… the findings also enlighten ongoing research on cancer therapies, exemplifying the impact of basic research on drug development.”

http://jasn.asnjournals.org/content/17/7/1807.full