EVI1 acts as an inducible negative-feedback regulator of NF-κB by inhibiting p65 acetylation

Xiangbin Xu, Chang Hoon Woo, Rachel R. Steere, Byung Cheol Lee, Yuxian Huang, Jing Wu, Jinjiang Pang, Jae Hyang Lim, Haidong Xu, Wenhong Zhang, Anuhya S. Konduru, Chen Yan, Michael T. Cheeseman, Steve D.M. Brown, Jian Dong Li

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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-κB-dependent inflammation remains unknown. In this article, we show that EVI1 negatively regulates nontypeable Haemophilus influenzae- and TNF-α-induced NF-κB-dependent inflammation in vitro and in vivo. EVI1 directly binds to the NF-κB 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-α in an NF-κB-dependent manner, thereby unveiling a novel inducible negative feedback loop to tightly control NF-κB-dependent inflammation. Thus, our study provides important insights into the novel role for EVI1 in negatively regulating NF-κB-dependent inflammation, and it may also shed light on the future development of novel anti-inflammatory strategies.

Original languageEnglish
Pages (from-to)6371-6380
Number of pages10
JournalJournal of Immunology
Volume188
Issue number12
DOIs
StatePublished - 15 Jun 2012

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