Downregulation of lipopolysaccharide response in Drosophila by negative crosstalk between the AP1 and NF-kappaB signaling modules.
IkappaB 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-kappaB. 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-kappaB target genes.
Kim
Taeil
T
Department of Biochemistry, Yonsei University, Seoul 120-749, South Korea.
Yoon
Joonsun
J
Cho
Hwansung
H
Lee
Wook-Bin
WB
Kim
Joon
J
Song
Young-Hwa
YH
Kim
Se Nyun
SN
Yoon
Jeong Ho
JH
Kim-Ha
Jeongsil
J
Kim
Young-Joon
YJ
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C488990:AttA protein, Drosophila; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C101626:Rel protein, Drosophila; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D006655:Histone Deacetylases