Authors

J. A. Liang; Y. Saad; T. H. Lei; J. Wang; D. F. Qi; Q. L. Yang; P. E. Kolattukudy;M. G. Fu

Comments

Authors: contact us about adding a copy of your work at [email protected]

Abbreviated Journal Title

J. Exp. Med.

Keywords

TUMOR-NECROSIS-FACTOR; UBIQUITIN-CONJUGATING ENZYME; SUPPRESSOR CYLD; IMMUNE-RESPONSES; MESSENGER-RNA; CELL-DEATH; ACTIVATION; ISOPEPTIDASE; INFLAMMATION; DEGRADATION; Immunology; Medicine, Research & Experimental

Abstract

The intensity and duration of macrophage-mediated inflammatory responses are controlled by proteins that modulate inflammatory signaling pathways. MCPIP1 (monocyte chemotactic protein-induced protein 1), a recently identified CCCH Zn finger-containing protein, plays an essential role in controlling macrophage-mediated inflammatory responses. However, its mechanism of action is poorly understood. In this study, we show that MCPIP1 negatively regulates c-Jun N-terminal kinase (JNK) and NF-kappa B activity by removing ubiquitin moieties from proteins, including TRAF2, TRAF3, and TRAF6. MCPIP1-deficient mice spontaneously developed fatal inflammatory syndrome. Macrophages and splenocytes from MCPIP1(-/-) mice showed elevated expression of inflammatory gene expression, increased JNK and I. B kinase activation, and increased polyubiquitination of TNF receptor-associated factors. In vitro assays directly demonstrated the deubiquitinating activity of purified MCPIP1. Sequence analysis together with serial mutagenesis defined a deubiquitinating enzyme domain and a ubiquitin association domain in MCPIP1. Our results indicate that MCPIP1 is a critical modulator of inflammatory signaling.

Journal Title

Journal of Experimental Medicine

Volume

207

Issue/Number

13

Publication Date

1-1-2010

Document Type

Article

Language

English

First Page

2959

Last Page

2973

WOS Identifier

WOS:000285503000017

ISSN

0022-1007

Download

Share

COinS
 

Accessibility Statement

This item was created or digitized prior to April 24, 2027, or is a reproduction of legacy media created before that date. It is preserved in its original, unmodified state specifically for research, reference, or historical recordkeeping. In accordance with the ADA Title II Final Rule, the University Libraries provides accessible versions of archival materials upon request. To request an accommodation for this item, please submit an accessibility request form.