| First Author | Xu X | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 12 | Pages | 6371-80 |
| PubMed ID | 22581859 | Mgi Jnum | J:188875 |
| Mgi Id | MGI:5442482 | Doi | 10.4049/jimmunol.1103527 |
| Citation | Xu X, et al. (2012) EVI1 acts as an inducible negative-feedback regulator of NF-kappaB by inhibiting p65 acetylation. J Immunol 188(12):6371-80 |
| abstractText | Inflammation is a hallmark of many important human diseases. Appropriate inflammation is critical for host defense; however, an overactive response is detrimental to the host. Thus, inflammation must be tightly regulated. The molecular mechanisms underlying the tight regulation of inflammation remain largely unknown. Ecotropic viral integration site 1 (EVI1), a proto-oncogene and zinc finger transcription factor, plays important roles in normal development and leukemogenesis. However, its role in regulating NF-kappaB-dependent inflammation remains unknown. In this article, we show that EVI1 negatively regulates nontypeable Haemophilus influenzae- and TNF-alpha-induced NF-kappaB-dependent inflammation in vitro and in vivo. EVI1 directly binds to the NF-kappaB p65 subunit and inhibits its acetylation at lysine 310, thereby inhibiting its DNA-binding activity. Moreover, expression of EVI1 itself is induced by nontypeable Haemophilus influenzae and TNF-alpha in an NF-kappaB-dependent manner, thereby unveiling a novel inducible negative feedback loop to tightly control NF-kappaB-dependent inflammation. Thus, our study provides important insights into the novel role for EVI1 in negatively regulating NF-kappaB-dependent inflammation, and it may also shed light on the future development of novel anti-inflammatory strategies. |
