Navigation Links
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 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.


'/>"/>

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

Related medicine news :

1. Joslin scientists identify important mechanism that affects the aging process
2. Researchers gain better understanding of mechanism behind tau spreading in the brain
3. Aggregating instead of stabilizing: New insights into the mechanisms of heart disease
4. Study supports urate protection against Parkinsons disease, hints at novel mechanism
5. Probing the mechanism of ADAM28-mediated cancer metastasis
6. Fruit flies reveal mechanism behind ALS-like disease
7. Scientists discover mechanism that promotes lung cancer growth and survival
8. Abnormal gene product associated with prostate cancer generated by unusual mechanism
9. New mechanism of bacterial pathogenesis discovered
10. Scientists identify new cancer stem cell mechanism
11. Zebrafish reveal promising mechanism for healing spinal cord injury
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/8/2016)... ... December 08, 2016 , ... STATEN ... been recognized for adherence to the highest standards of trauma, maternity, cancer and ... the center's president and CEO, Dr. Daniel Messina. , Among the recognitions, the ...
(Date:12/8/2016)... ... December 08, 2016 , ... Vida Health, the digital ... B led by Canvas Ventures . Other investors include Nokia Growth Partners (NGP) ... platform to serve more consumers who are managing chronic conditions or simply ...
(Date:12/8/2016)... FL (PRWEB) , ... December 08, 2016 , ... Coppin ... business owners and families in and around the Cape Coral area, is embarking on ... Chapin Food Bank of Southwest Florida. , The Harry Chapin Food Bank of Southwest ...
(Date:12/7/2016)... , ... December 07, 2016 , ... ... Medicine will have the unique opportunity to get hands-on experience in an ... school students an immersive experience to gain invaluable, real-life medical skills that are ...
(Date:12/7/2016)... ... December 07, 2016 , ... Wavelink, an industry ... Control through a new partnership with Splashtop Inc. This remote control for Android ... to help businesses maximize their uptime and productivity. , Wavelink offers powerful enterprise ...
Breaking Medicine News(10 mins):
(Date:12/8/2016)... 8, 2016   TriNetX , the health ... Hospital signed a membership agreement to join ... of new cures. The TriNetX network ... million patients globally, biopharmaceutical companies and contract research ... protocol design, site selection, patient recruitment, and collaborative ...
(Date:12/8/2016)... Dec. 8, 2016  A new study by a ... use of opioid therapy to treat chronic pain is ... of more harmful consequences, including death. Palliative ... Zankhana Mehta , M.D., authored the study which ... opioid therapy. The study was published in the December ...
(Date:12/8/2016)... -- Mederi Therapeutics Inc . hat die behördliche Zulassung durch die ... Refluxerkrankung (GERD) – in China angekündigt. ... ... Live Stretta procedure performed and broadcast during the ... at Wuhan Union Hospital ...
Breaking Medicine Technology: