Nature: How OTUD7B Saves TRAF3
TRAF3, TNF receptor-associated factor 3, is a protein that in humans is encoded by the TRAF3 gene. TRAF3 belongs to the TNFR family member which is important for the activation of the immune response. TNFR3 is found to be a critical component of the lymphotoxin-beta receptor (LTbetaR) signaling complex, which induces NF-kappaB activation and cell death initiated by LTbeta ligation.
In the nick of time, OTUD7B could stretch the vital hand to help enzyme TRAF3. According to Nature, scientists identified TRAF3's savior and demonstrated its function mechanism: t hey found the OTUD7B worked as the protector of TRAF3.
Understanding how the degradation of TRAF3 is regulated is extremely important as 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.
The NF-kB pathway was found in past studies. NF-kB, a family of proteins, turns on genes that are important in immune response, inflammation, cell growth and survival, and development. In this study, they found that NF-kB activity increases when TRAF3 has the homing targets, or ubiquitins, attached to it and is destroyed by the proteasome.
TRAF3 activates the same destructive mechanism to against NIK when it is attacked. NIK is a protein that's central to NF-kB activity, by tagging it with ubiquitins.
But what regulates TRAF3's destruction and controls NF-kB in the process?
For the question, scientists thought enzyme OTUD7B as a candidate. OTUD7B was genetically quite similar to another enzyme active in the canonical pathway for NF-kB—A20. But A20 is not active in the non-canonical NFkB pathway.
Further researchers found something by applying inducers of the non-canonical NK-kB pathway to cells derived from OTUD7B-deficient mice: the degradation of TRAF3 and accumulation of its target—NIK and ubiquitination of TRAF3. Cells with OTUD7B intact suppressed non-canonical NF-kB signaling.
A20-knowed-out mice caused biological changes, as knocking out the OTUD7B gene did, but it did not kill the mice. As a result, the knockout mice had an improved immune response to the lethal intestinal bacterial pathogen C. rodentium, while the suppressed mice had greatly increased lymphoid cell growth in the lining of the intestine and hyper-responsiveness to antigens by B cells.
Article Link: Nature: How OTUD7B Saves TRAF3
