Featured Research

from universities, journals, and other organizations

Mechanism discovered for attaching an 'on' switch that helps cells accessorize proteins

Date:
June 19, 2014
Source:
St. Jude Children's Research Hospital
Summary:
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 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.

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.

Related Articles


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 Schulman, Ph.D., a member of the St. Jude Department of Structural Biology and a Howard Hughes Medical Institute (HHMI) investigator.

Schulman and her colleagues study the machinery that manages the accessorizing process, whether the accessory is NEDD8 or a different small protein called ubiquitin. Ubiquitin accessorizes proteins though a process known as ubiquitination. Cullin-RING, which NEDD8 accessorizes, is a major command center of ubiquitination.

This study builds on an observation first author Daniel Scott, Ph.D., made shortly after joining Schulman’s laboratory in 2006. Scott, an HHMI research specialist III, showed that while ubiquitin could be coaxed into binding to and accessorizing cullin-RING, NEDD8 was the preferred partner.

Scott used a technique called X-ray crystallography to capture a crystal structure that explained why. In the process, investigators determined for the first time that different components of the ubiquitination machinery work cooperatively to align NEDD8 and cullin-RING. That alignment promotes the transfer of NEDD8 rather than ubiquitin to the proper site on cullin-RING. The transfer of NEDD8 allows other proteins to be accessorized with ubiquitin.

The mechanism outlined in this research establishes a paradigm for understanding protein regulation in cells, Schulman said. “This research sets the stage for broadly understanding this key aspect of protein regulation in cells,” Scott said.


Story Source:

The above story is based on materials provided by St. Jude Children's Research Hospital. Note: Materials may be edited for content and length.


Cite This Page:

St. Jude Children's Research Hospital. "Mechanism discovered for attaching an 'on' switch that helps cells accessorize proteins." ScienceDaily. ScienceDaily, 19 June 2014. <www.sciencedaily.com/releases/2014/06/140619142058.htm>.
St. Jude Children's Research Hospital. (2014, June 19). Mechanism discovered for attaching an 'on' switch that helps cells accessorize proteins. ScienceDaily. Retrieved April 18, 2015 from www.sciencedaily.com/releases/2014/06/140619142058.htm
St. Jude Children's Research Hospital. "Mechanism discovered for attaching an 'on' switch that helps cells accessorize proteins." ScienceDaily. www.sciencedaily.com/releases/2014/06/140619142058.htm (accessed April 18, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Saturday, April 18, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Un-Bee-Lievable: Bees on the Loose After Washington Truck Crash

Un-Bee-Lievable: Bees on the Loose After Washington Truck Crash

Reuters - US Online Video (Apr. 17, 2015) A truck carrying honey bees overturns near Lynnwood, Washington, spreading boxes of live bees across the highway. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Our Love Of Puppy Dog Eyes Explained By Science

Our Love Of Puppy Dog Eyes Explained By Science

Newsy (Apr. 17, 2015) Researchers found a spike in oxytocin occurs in both humans and dogs when they gaze into each other&apos;s eyes. Video provided by Newsy
Powered by NewsLook.com
Dog Flu Spreading in Midwestern States

Dog Flu Spreading in Midwestern States

AP (Apr. 17, 2015) Dog flu is spreading in several Midwestern states. Dog daycare centers and veterinary offices are taking precautions. (April 17) Video provided by AP
Powered by NewsLook.com
Raw: Rare Whale Spotted in Gulf of Mexico

Raw: Rare Whale Spotted in Gulf of Mexico

AP (Apr. 17, 2015) Researchers from the E/V Nautilus had quite a surprise Tuesday, when a curious sperm whale swam around their remotely operated vehicle in the Gulf of Mexico. Cameras captured the encounter. (April 17) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins