| First Author | Zhang Z | Year | 2013 |
| Journal | Nat Immunol | Volume | 14 |
| Issue | 2 | Pages | 172-8 |
| PubMed ID | 23222971 | Mgi Jnum | J:192552 |
| Mgi Id | MGI:5465368 | Doi | 10.1038/ni.2492 |
| Citation | Zhang Z, et al. (2012) The E3 ubiquitin ligase TRIM21 negatively regulates the innate immune response to intracellular double-stranded DNA. Nat Immunol 14(2):172-8 |
| abstractText | DDX41 is a sensor of intracellular double-stranded DNA (dsDNA) in myeloid dendritic cells (mDCs) that triggers a type I interferon response via the signaling adaptor STING. We identified the E3 ligase TRIM21 as a DDX41-interacting protein and found that knockdown of or deficiency in TRIM21 resulted in enhanced type I interferon responses to intracellular dsDNA and DNA viruses. Overexpression of TRIM21 resulted in more degradation of DDX41 and less production of interferon-beta (IFN-beta) in response to intracellular dsDNA. The SPRY-PRY domain of TRIM21 interacted with the DEADc domain of DDX41. Lys9 and Lys115 of DDX41 were the targets of TRIM21-mediated ubiquitination. TRIM21 is therefore an interferon-inducible E3 ligase that induces the Lys48 (K48)-linked ubiquitination and degradation of DDX41 and negatively regulates the innate immune response to intracellular dsDNA. |
