EVI1 Acts as an Inducible Negative-Feedback Regulator of NF-kappa B by Inhibiting p65 Acetylation

Title
EVI1 Acts as an Inducible Negative-Feedback Regulator of NF-kappa B by Inhibiting p65 Acetylation
Author(s)
생빈 수[생빈 수]우창훈레이첼 스티어[레이첼 스티어]이병철[이병철]유센 황[유센 황]징 위[징 위]진장 팡[진장 팡]임재향[임재향]하이동 수[하이동 수]웬홍 장[웬홍 장]아누야 콘두루[아누야 콘두루]첸 얀[첸 얀]마이클 치즈맨[마이클 치즈맨]스티브 브라운[스티브 브라운]젠동 리[젠동 리]
Keywords
NONTYPABLE HAEMOPHILUS-INFLUENZAE; OBSTRUCTIVE PULMONARY-DISEASE; ACUTE MYELOID-LEUKEMIA; ZINC-FINGER PROTEIN; MYELOPEROXIDASE ACTIVITY; BINDING PROTEIN; OTITIS-MEDIA; CO-REPRESSOR; GENOME-WIDE; ACTIVATION
Issue Date
201206
Publisher
AMER ASSOC IMMUNOLOGISTS
Citation
JOURNAL OF IMMUNOLOGY, v.188, no.12, pp.6371 - 6380
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-kappa B-dependent inflammation remains unknown. In this article, we show that EVI1 negatively regulates nontypeable Haemophilus influenzae-and TNF-alpha-induced NF-kappa B-dependent inflammation in vitro and in vivo. EVI1 directly binds to the NF-kappa B 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-kappa B-dependent manner, thereby unveiling a novel inducible negative feedback loop to tightly control NF-kappa B-dependent inflammation. Thus, our study provides important insights into the novel role for EVI1 in negatively regulating NF-kappa B-dependent inflammation, and it may also shed light on the future development of novel anti-inflammatory strategies. The Journal of Immunology, 2012, 188: 6371-6380.
URI
http://hdl.handle.net/YU.REPOSITORY/28058http://dx.doi.org/10.4049/jimmunol.1103527
ISSN
0022-1767
Appears in Collections:
의과대학 > 약리학교실 > Articles
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE