| First Author | Chen J | Year | 2015 |
| Journal | J Immunol | Volume | 194 |
| Issue | 3 | Pages | 1292-303 |
| PubMed ID | 25548215 | Mgi Jnum | J:295331 |
| Mgi Id | MGI:6458622 | Doi | 10.4049/jimmunol.1402593 |
| Citation | Chen J, et al. (2015) The endoplasmic reticulum adaptor protein ERAdP initiates NK cell activation via the Ubc13-mediated NF-kappaB pathway. J Immunol 194(3):1292-303 |
| abstractText | NK cells play a pivotal role in innate immune responses against pathogenic infections. However, the underlying mechanisms driving defined NK functions remain largely elusive. In this study, we identified a novel endoplasmic reticulum (ER) membrane protein, ER adaptor protein (ERAdP), which is constitutively expressed in human and mouse NK cells. ERAdP is expressed at low levels in peripheral NK cells of hepatitis B virus-associated hepatocellular carcinoma patients. We show that ERAdP initiates NK cell activation through the NF-kappaB pathway. Notably, ERAdP interacts with ubiquitin-conjugating enzyme 13 (Ubc13) to potentiate its charging activity. Thus, ERAdP augments Ubc13-mediated NF-kappaB essential modulator ubiquitination to trigger the Ubc13-mediated NF-kappaB pathway, leading to NK cell activation. Finally, ERAdP transgenic mice display hyperactivated NK cells that are more resistant to pathogenic infections. Therefore, understanding the mechanism of ERAdP-mediated NK cell activation will provide strategies for treatment of infectious diseases. |
