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PMID:7959007

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Citation

Shimizu, H and Yamamoto, K (1994) NF-kappa B and C/EBP transcription factor families synergistically function in mouse serum amyloid A gene expression induced by inflammatory cytokines. Gene 149:305-10

Abstract

Mouse serum amyloid A proteins (SAA) are encoded by multiple genes and the expression of these SAA genes is highly induced during inflammation. We demonstrate that the expression of one of SAA genes (SAA3) is induced by interleukin-1 (IL-1), and that other inflammatory cytokines such as IL-6 and leukemia inhibitory factor, while they themselves are without any effects, enhanced IL-1 induced SAA3 gene expression. The results of mutational analysis on the SAA3 promoter indicate that both the NF-kappa B and C/EBP transcription factor-binding motifs are essential for cytokine-induced SAA3 gene expression in Hep3B cells. To study further roles of NF-kappa B and C/EBP transcription factor family members in SAA3 gene activation, expression vectors for NF-kappa B subunits (p50 and p65) and C/EBP family members (C/EBP-alpha and NFIL-6, also called C/EBP-beta) were co-transfected into Hep3B hepatoma and F9 embryonic carcinoma cells. The results show that, while the expression of p65 alone strongly transactivated a SAA3 gene, p50 did not induce a significant transactivation, and NFIL-6 and C/EBP-alpha induced only a marginal transactivation when expressed alone. However, the co-expression of p50 or p65 with C/EBP family members did result in the efficient induction of SAA3 gene expression, indicating that the synergy between NF-kappa B and C/EBP transcription factor families is essential for SAA3 gene expression during inflammation.

Links

PubMed

Keywords

Animals; Base Sequence; Binding Sites; CCAAT-Enhancer-Binding Proteins; Cytokines/pharmacology; DNA Mutational Analysis; DNA-Binding Proteins/metabolism; Drug Synergism; Gene Expression Regulation/drug effects; Growth Inhibitors/biosynthesis; Inflammation/metabolism; Interleukin-1/pharmacology; Interleukin-6/pharmacology; Leukemia Inhibitory Factor; Lymphokines/biosynthesis; Mice; Molecular Sequence Data; NF-kappa B/metabolism; Nuclear Proteins/metabolism; Promoter Regions, Genetic; Serum Amyloid A Protein/biosynthesis; Serum Amyloid A Protein/genetics; Transcription Factors/metabolism; Transcription, Genetic; Transcriptional Activation

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:LIF

acts_upstream_of_or_within

GO:0010628: positive regulation of gene expression

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96536
MGI:MGI:96559

P

Seeded From UniProt

complete

MOUSE:NFKB1

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P19838

F

Seeded From UniProt

complete

MOUSE:CEBPB

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P17676

F

Seeded From UniProt

complete

MOUSE:CEBPB

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P17676

P

Seeded From UniProt

complete

MOUSE:TF65

enables

GO:0000977: RNA polymerase II transcription regulatory region sequence-specific DNA binding

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q04206

F

Seeded From UniProt

complete

HUMAN:NFKB1

enables

GO:0046982: protein heterodimerization activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NFKB1

enables

GO:0000977: RNA polymerase II regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TF65

enables

GO:0046982: protein heterodimerization activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TF65

enables

GO:0000977: RNA polymerase II regulatory region sequence-specific DNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:IL6

acts_upstream_of_or_within

GO:0010628: positive regulation of gene expression

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:96536
MGI:MGI:96787

P

Seeded From UniProt

complete

MOUSE:NFKB1

enables

GO:0000977: RNA polymerase II regulatory region sequence-specific DNA binding

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P19838

F

Seeded From UniProt

complete

MOUSE:NFKB1

enables

GO:0046982: protein heterodimerization activity

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P19838

F

Seeded From UniProt

complete

MOUSE:TF65

enables

GO:0000977: RNA polymerase II regulatory region sequence-specific DNA binding

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q04206

F

Seeded From UniProt

complete

MOUSE:TF65

enables

GO:0046982: protein heterodimerization activity

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:Q04206

F

Seeded From UniProt

complete

MOUSE:CEBPA

acts_upstream_of_or_within

GO:0045944: positive regulation of transcription by RNA polymerase II

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P49715

P

Seeded From UniProt

complete

MOUSE:SAA3

acts_upstream_of_or_within

GO:0071347: cellular response to interleukin-1

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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