Regulation of expression of the interleukin 6 gene: structure and function of the transcription factor NF-IL6.
The interleukin 6 (IL-6) promoter is rapidly and transiently activated by other cytokines, including IL-1 and tumour necrosis factor (TNF), as well as by phorbol esters and cyclic AMP agonists. Studies using promoter mutants suggested that an IL-1-responsive element mapped within the -180 to -123 region of the IL-6 promoter. A nuclear factor (NF-IL6) that recognized a unique sequence containing an inverted repeat, ACATTGCACAATCT, was identified within the region. Direct cloning of the human NF-IL6 revealed its similarity to C/EBP, a liver- and adipose tissue-specific transcription factor. C/EBP and NF-IL6 recognize the same nucleotide sequence, but exhibit distinct patterns of expression. NF-IL6 is expressed at a low level in normal tissues, but is rapidly and drastically induced by bacterial lipopolysaccharide (LPS) or inflammatory cytokines such as IL-1, TNF and IL-6. Recently, NF-IL6 has been shown to be identical to IL-6DBP, the DNA-binding protein which is responsible for IL-6-mediated induction of several acute-phase proteins. Evidence that NF-IL6 DNA-binding activity is increased after IL-6 stimulation without increased NF-IL6 protein synthesis demonstrates the importance of post-translational modification. There are some results indicating that phosphorylation is involved in transcriptional and binding activities of NF-IL6. Taken together, these findings indicate that NF-IL6 may be an important transcription factor on the signal transduction pathways of IL-1 and IL-6.
Akira
S
S
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Isshiki
H
H
Nakajima
T
T
Kinoshita
S
S
Nishio
Y
Y
Natsuka
S
S
Kishimoto
T
T
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry* / Q000502:physiology; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry* / Q000502:physiology
D000209:Acute-Phase Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D014157:Transcription Factors