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Mechanism discovered for attaching an 'on' switch that helps cells accessorize proteins
Date:6/19/2014

(MEMPHIS, Tenn. June 19, 2014) St. Jude Children's Research Hospital scientists have discovered how an important "on" switch is attached to the machinery that cells rely on to adapt thousands of proteins to meet changing conditions. The research appears in the current issue of the journal Cell.

The switch is a small protein called NEDD8. Problems with NEDD8 have been associated with several cancers, developmental disorders and infectivity of the human immunodeficiency virus (HIV), which causes AIDS. Drugs that target NEDD8 are in anti-cancer clinical trials. The ability of HIV to evade the anti-viral immune response depends in part on the ability of the virus to hijack the NEDD8 machinery.

NEDD8 is also a key component of the machinery that cells use to adapt to changing conditions. Just as individuals adapt to changes in their environment by donning gloves, boots, hats and other accessories, cells adapt by "accessorizing" proteins to modify their function.

NEDD8 is a specialized accessory. It functions as the "on" switch for accessorizing 10 to 20 percent of the thousands of proteins that do the work of cells. Those accessories mark some proteins for elimination, others for a change in function and others for relocation to different parts of the cell. Until now, however, how NEDD8 slipped into position was unknown.

Researchers showed how part of the machinery for accessorizing proteins, a component called cullin-RING, is first modified by NEDD8. The addition of NEDD8 transforms the ability of cullin-RING to accessorize other proteins. Those proteins are involved in important biological functions such as cell division, immune response and embryonic development.

"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 corresponding author Brenda Schulm
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Contact: Carrie Strehlau
carrie.strehlau@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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