|A20/TNFAIP3 is an important negative regulator of proinflammatory signaling pathways, including NF-κB signaling.
A20 deactivates RIP by removing Lys63-linked polyubiquitin, and then targets RIP for degradation by adding Lys48-linked polyubiquitin (1). A20 destruction of RIP interferes with NF-κB signaling. A20 upregulation appears to be a marker of NF-κB activation and its impending down regulation.
Interestingly A20 cleavage fragments can accompany NF-κB activation (2), although their significance remains to be elucidated. Nevertheless, the appearance of cleavage fragments has perked interest among researchers since cleavage fragments often have profound roles in signaling pathways such as caspase cleavage during apoptosis.
The A20 monoclonal antibody (mAb) clone 59A426 has been instrumental in discovering nuances of NF-κB regulation and key to defining A20 biology (2). For example, mAb 59A426 helped demonstrate that introducing wild-type A20 genes into B cell lymphomas with mutated A20 attenuated tumorigenicity. Likewise, mAb 59A426 helped show that A20 may play a role in gliomas, where glioma stem cells had higher A20 expression than non-stem cell gliomas.
1. Evans PC. Expert Reviews in Mol Med DOI: 10.1017/S1462399405009415 (2005).
2. A20 mAb 59A426 (IMG-161A) IMGENEX Data sheet, see Product Citations.
Anti-A20/TNFAIP3 (Clone 59A426)