Localization of A20 to a lysosome-associated compartment and its role in NFκB signaling

被引：36

作者：

Li, Lianyun ^{[1
]}

Hailey, Dale W. ^{[2
]}

Soetandyo, Nia ^{[1
]}

Li, Wei ^{[1
]}

Lippincott-Schwartz, Jennifer ^{[2
]}

Shu, Hong-bing ^{[3
]}

Ye, Yihong ^{[1
]}

机构：

[1] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA

[2] NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA

[3] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2008年 / 1783卷 / 06期

关键词：

A20; lysosomal degradation; ubiquitin; NF kappa B; deubiquitinating enzyme;

D O I：

10.1016/j.bbamcr.2008.01.029

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

A20 is a tumor necrosis factor (TNF)-inducible zinc finger protein that contains both ubiquitinating and deubiquitinating activities. A20 negatively regulates NF kappa B (nuclear factor kappa B) signaling induced by TNF receptor family and Toll-like receptors, but the mechanism of A20 action is poorly defined. Here we show that a fraction of endogenous and ectopically expressed A20 is localized to an endocytic membrane compartment that is in association with the lysosome. The lysosomal association of A20 requires its carboxy terminal zinc finger domains, but is independent of its ubiquitin-modifying activities. Interestingly, A20 mutants defective in membrane association also contain reduced NF kappa B inhibitory activity. These findings suggest the involvement of a lysosome-associated mechanism in A20-dependent termination of NF kappa B signaling. Published by Elsevier B.V.

引用

页码：1140 / 1149

页数：10

共 39 条

[1]

A20 and A20-binding proteins as cellular inhibitors of nuclear factor-κB-dependent gene expression and apoptosis [J].