Showing papers by "Shizuo Akira published in 1995"

Targeted Disruption of the IL‐6 Related Genes: gp130 and NF‐IL‐6

Abstract: IL-6 is a multifunctional cytokine that plays a major role in inflammatory responses (Kishimoto 1989. 1994. Akira et al. 1993). IL-6 exerts multiple biological functions such as growth promotion, growth inhibition, specific gene expression and induction of differentiation, depending on the target cells. These activities include (1) terminal differentiation (secretion of immunoglobulins) of B cells; (2) growth promotion of B-lineage cells (myeloma/plasmacytoma/hybridonia cells); (3) formation of multipotential colonies of hematopoietic stem cells; (4) induction of acute*phase proteins in the liver; (.*>) differentiation and activation of T cells and niacrophages; and (6) differentiation of neuronal cells. To mediate the biological activities. IL-6 binds to a specific cell surface receptor complex which consists of two functionally different types of subunits; a ligandbinding IL-6 receptor (1L-6R) chain, and a non ligand-binding signal transducer gp!30. gpl30 is now known to be shared as a signal-transducing receptor component by IL-6. leukemia inhibitory factor (LIF). oncostatin M (OSM). IL-11, ciliary neurotrophic factor (CNTF). and cardiotrophin-l (CT-I). All these ligands induce homoor heterodimerization of gpl30, which initiates the cytoplasmic signaling cascades by activating asstKiated protein tyrosine kinases in the JAK family. From the analyses of c/.v-regulatory elements in the acute-phase protein genes and the nuclear factors binding to these elements, two transcription factors, NF-IL6 and APRF/STAT3. are identified as nuclear targets in gpl30-mediated signaling.

Identification of a transcriptional regulatory factor for human aromatase cytochrome P450 gene expression as nuclear factor interleukin-6 (NF-IL6), a member of the CCAAT/enhancer-binding protein family.

Abstract: Human aromatase cytochrome P450 catalyzes the ultimate reaction in the estrogen biosynthetic pathway by coupling with another enzyme, NADPH-cytochrome P450 reductase, in the endoplasmic reticulum. The expression of the gene encoding the enzyme (CYP19) is regulated, in part, by tissue-specific promoters through the use of alternative-splicing mechanisms. Recently, we have localized a transcriptional activating element at positions –2141 to –2115 relative to the major cap site of the gene, by transient expression analyses in human BeWo choriocarcinoma cells using the bacterial chloramphenicol acetytransferase reporter gene ligated with CYP19 promoter sequences which regulate expression in this tissue. Here, we report the isolation of a cDNA encoding a DNA-binding protein which binds specifically to the regulatory element. The deduced amino-acid sequence of the insert is identical to that corresponding to the DNA-binding domain and the dimerization domain of a transcription factor, nuclear factor interleukin-6 (NF-IL6), a member of the CCAAT/enhancer-binding protein (C/EBP) family. Studies using specific antibodies against members of the C/EBP family demonstrate that NF-IL6 is the major nuclear factor binding to the regulatory element in BeWo cells; nevertheless, C/EBP α also seems to be involved. Disruption of the NF-IL6-binding site within the regulatory element resulted in the disappearance of the transcriptional enhancing activity of the element, indicating that NF-IL6 is at least one of the nuclear factor(s) which enhances transcription through binding to the cis-acting element. These results indicate the intrinsic importance of NF-IL6 in the transcriptional regulation of CYP19 expression.

Transcription Factor APRF

Abstract: Mammal transcription factor APRF, process for the preparation of it, DNAs encoding the said product, replication and expression vector comprising the said DNA, host cells transformed or transfected with the said replication and expression vector, evaluating and screening method for searching an inhibitory agent on the function of APRF and an inhibitory agent against the function of the said APRF. The peptide of the resent invention (APRF) may be useful for complement or suppression of the function of APRF, screening an inhibitory agent against the function of APRF. Inhibiting agent containing the said product as active ingredient of the present invention may be also useful for treatment of diseases related cytokine such as IL-6 i.e. inflammatory diseases.

Nucleic acids encoding transcription factor APRF (acute phase response factor)

Abstract: Mammal transcription factor APRF, process for the preparation of it, DNAs encoding the product, replication and expression vector comprising the DNA, host cells transformed or tranfected with the replication and expression vector, evaluating and screening method for searching an inhibitory agent on the function of APRF and an inhibitory agent against the function of the APRF. The peptide of the present invention (APRF) may be useful for complement or suppression of the function of APRF, screening an inhibitory agent against the function of APRF. Inhibiting agent containing the product as active ingredient of the present invention may be also useful for treatment of diseases related to cytokine such as IL-6, i.e., inflammatory diseases.