Attaching an “on” switch for protein regulation

Brenda Schulman, PhD, and Daniel Scott, PhD

Just as accessories like boots and gloves help humans adapt to their environment, St. Jude Children’s Research Hospital scientists have discovered a mechanism that serves as an “on” switch for the machinery that helps proteins accessorize.

These “accessories” are small molecules that cells rely on to adapt to changing conditions. When the “accessories” are attached to proteins that do the work of cells, they can change the fate and function of those proteins.

The study involved a specialized accessory called NEDD8. NEDD8 is the “on” switch for the machinery that accessorizes 10 to 20 percent of the thousands of proteins that work in cells. Researchers have discovered the mechanism that ensures NEDD8 is properly positioned on that machinery.

“This discovery is a major advance in understanding the machinery cells use to regulate an astonishingly vast number of proteins they depend on as well as the diseases that arise when the system malfunctions,” said the study’s corresponding author Brenda Schulman, PhD, Structural Biology, and a Howard Hughes Medical Institute investigator. Problems with NEDD8 have been associated with cancer and other diseases, including the infectiousness of HIV, the virus that causes AIDS.

The research appears in the scientific journal Cell.

June 19, 2014

Read the press release.