Downregulation of lipopolysaccharide response in drosophila by negative crosstalk between the AP1 and NF-κB signaling modules

Taeil Kim, Joonsun Yoon, Hwansung Cho, Wook Bin Lee, Joon Kim, Young Hwa Song, Se Nyun Kim, Jeong Ho Yoon, Jeongsil Kim-Ha, Young Joon Kim

Research output: Contribution to journalArticlepeer-review

99 Citations (Scopus)

Abstract

IκB kinase (IKK) and Jun N-terminal kinase (Jnk) signaling modules are important in the synthesis of immune effector molecules during innate immune responses against lipopolysaccharide and peptidoglycan. However, the regulatory mechanisms required for specificity and termination of these immune responses are unclear. We show here that crosstalk occurred between the drosophila Jnk and IKK pathways, which led to downregulation of each other's activity. The inhibitory action of Jnk was mediated by binding of drosophila activator protein 1 (AP1) to promoters activated by the transcription factor NF-κB. This binding led to recruitment of the histone deacetylase dHDAC1 to the promoter of the gene encoding the antibacterial protein Attacin-A and to local modification of histone acetylation content. Thus, AP1 acts as a repressor by recruiting the deacetylase complex to terminate activation of a group of NF-κB target genes.

Original languageEnglish
Pages (from-to)211-218
Number of pages8
JournalNature Immunology
Volume6
Issue number2
DOIs
Publication statusPublished - 2005 Feb

Bibliographical note

Funding Information:
We thank W.J. Lee (Ewha Womans University, Seoul, Korea) for providing immunocompetent SL2 cells; J.L. Imler (Institute de Biologie Moleculaire et Cellulaire, Strasbourg, France) for providing reporter plasmids; and J.M. Park (University of California at San Diego) for helpful advice. BRB-ArrayTools v3.X developed by R. Simon (National Cancer Institutes of Health, Bethesda, Maryland) and A. Peng Lam (EMMES, Rockville, Maryland) were used for microarray analyses. Supported by the Creative Research Initiatives Program of the Korean Ministry of Science and Technology (Y.-J.K.).

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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