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UT MD Anderson scientists find protein that reins in runaway network
Date:1/22/2013

HOUSTON Marked for death with molecular tags that act like a homing signal for a cell's protein-destroying machinery, a pivotal enzyme is rescued by another molecule that sweeps the telltale targets off in the nick of time.

The enzyme, called TRAF3, lives on to control a molecular network that's implicated in a variety of immune system-related diseases if left to its own devices.

The University of Texas MD Anderson scientists identified TRAF3's savior and demonstrated how it works in a paper published online Sunday in Nature.

By discovering the role of OTUD7B as TRAF3's protector, Shao-Cong Sun, Ph.D., professor in MD Anderson's Department of Immunology, and colleagues filled an important gap in their understanding of a molecular pathway discovered in Sun's lab.

"Genetic defects or constant degradation of TRAF3 lead to the uncontrolled activity of what we call the non-canonical NF-kB pathway. This in turn, is associated with autoimmune diseases and lymphoid malignancies such as multiple myeloma and B cell lymphomas," Sun said. "Understanding how the degradation of TRAF3 is regulated is extremely important."

Dodging annihilation, turning the tables

Sun earlier found an alternative, or non-canonical, pathway that activates the protein complex known as NF-kB, a family of proteins that turns on genes that are important in immune response, inflammation, cell growth and survival, and development.

They found that NF-kB activity increases when TRAF3 has the homing targets, called ubiquitins, attached to it and is destroyed by the proteasome, a complex of proteins that hunts down ubiquitin-decorated proteins.

When TRAF3 evades attack, it turns that same destructive mechanism against NIK, a protein that's central to NF-kB activity, by tagging it with ubiquitins.

The key question was: What regulates TRAF3's destruction and, in the process, controls NF-kB?

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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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