期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 281, 期 47, 页码 36060-36070出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M602383200
关键词
-
资金
- NIDDK NIH HHS [DK069344, DK43351] Funding Source: Medline
Centaurin beta 1 (CENTB1), a GTPase-activating protein, is a member of the ADP-ribosylation factor family encoded by a gene located on the short arm of human chromosome 17. A yeast two-hybrid screen first suggested a direct interaction between CENTB1 and NOD2. Co-immunoprecipitation experiments confirmed direct interaction between CENTB1 and NOD2 and demonstrated similar interaction between CENTB1 and NOD1. We also demonstrate that endogenous CENTB1 interacts with endogenous NOD2 and NOD1 in SW480 and HT-29 intestinal epithelial cells. CENTB1 partially co-localized with NOD2 and NOD1 proteins in the cytoplasm of mammalian cells. CENTB1 expression in epithelial cells was highly induced by tumor necrosis factor alpha,interleukin 1 beta, and the NOD1 and NOD2 ligands (gamma-D-glutamyl-meso-diaminopimelic acid and muramyl dipeptide, respectively). In addition, CENTB1 mRNA level is increased in the inflamed mucosa of patients with inflammatory bowel disease. Functionally, CENTB1 overexpression inhibited NOD1- and NOD2-dependent activation of NF-kappa B, whereas small inhibitory RNA against CENTB1 increased NF-kappa B activation following NOD1- or NOD2-mediated recognition of the bacterial components gamma-D-glutamyl-meso-diaminopimelic acid and muramyl dipeptide, respectively. In contrast, CENTB1 had no effect on NF-kappa B activation induced by Toll-like receptors. In conclusion, CENTB1 selectively down-regulates NF-kappa B activation via NODs pathways, creating a feedback loop and suggesting a novel role of CENTB1 in innate immune responses to bacteria and inflammatory responses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据