A Nuclear Factor for Interleukin-6 Expression (NF-IL6) and the Glucocorticoid Receptor Synergistically Activate Transcription of the Rat Alpha 1-acid Glycoprotein Gene Via Direct Protein-protein Interaction

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1993 Mar 1

PMID 8441418

Citations 61

Authors

Y Nishio

H Isshiki

T Kishimoto

S Akira

Affiliations

Soon will be listed here.

Abstract

The acute-phase reaction is accompanied by an increase in a variety of serum proteins, named acute-phase proteins. The synthesis of these proteins is synergistically controlled by glucocorticoids and inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha. Recently, we have cloned nuclear factor-IL-6 (NF-IL6), a transcription factor that activates the IL-6 gene, and have demonstrated its involvement in the expression of acute-phase-protein genes. We report here an analysis of the molecular mechanisms by which inflammatory cytokines and glucocorticoid act synergistically to activate expression of the rat alpha 1-acid glycoprotein (AGP) gene. We found that NF-IL6 and ligand-activated rat glucocorticoid receptor acted synergistically to transactivate the AGP gene and that maximal transcriptional activation of the AGP gene required expression of both intact NF-IL6 and rat glucocorticoid receptor. Surprisingly, however, transcriptional synergism was still observed even when one of the two factors lacked either its DNA-binding or transcriptional-activation function. We present evidence for a direct protein-protein interaction between these two distinct transcription factors and propose that this may be responsible for the synergistic activation of the rat AGP gene.

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References

Isshiki H, Akira S, TANABE O, Nakajima T, Shimamoto T, Hirano T . Constitutive and interleukin-1 (IL-1)-inducible factors interact with the IL-1-responsive element in the IL-6 gene. Mol Cell Biol. 1990; 10(6):2757-64. PMC: 360636. DOI: 10.1128/mcb.10.6.2757-2764.1990. View

Baumann H, Gauldie J . Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulating factors and other mediators of inflammation. Mol Biol Med. 1990; 7(2):147-59. View

Won K, Baumann H . The cytokine response element of the rat alpha 1-acid glycoprotein gene is a complex of several interacting regulatory sequences. Mol Cell Biol. 1990; 10(8):3965-78. PMC: 360907. DOI: 10.1128/mcb.10.8.3965-3978.1990. View

Akira S, Hirano T, Taga T, Kishimoto T . Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990; 4(11):2860-7. View

Diamond M, Miner J, Yoshinaga S, Yamamoto K . Transcription factor interactions: selectors of positive or negative regulation from a single DNA element. Science. 1990; 249(4974):1266-72. DOI: 10.1126/science.2119054. View

Jonat C, Rahmsdorf H, Park K, Cato A, Gebel S, Ponta H . Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell. 1990; 62(6):1189-204. DOI: 10.1016/0092-8674(90)90395-u. View

Chambard J, Sun Y, Smeal T, Schmidt T, Drouin J, Karin M . Transcriptional interference between c-Jun and the glucocorticoid receptor: mutual inhibition of DNA binding due to direct protein-protein interaction. Cell. 1990; 62(6):1205-15. DOI: 10.1016/0092-8674(90)90396-v. View

Schule R, Rangarajan P, Kliewer S, Ransone L, Bolado J, Yang N . Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell. 1990; 62(6):1217-26. DOI: 10.1016/0092-8674(90)90397-w. View

Poli V, Mancini F, Cortese R . IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell. 1990; 63(3):643-53. DOI: 10.1016/0092-8674(90)90459-r. View

10.

Chang C, Chen T, Lei H, Chen D, Lee S . Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family. Mol Cell Biol. 1990; 10(12):6642-53. PMC: 362942. DOI: 10.1128/mcb.10.12.6642-6653.1990. View

11.

Brasier A, Ron D, Tate J, Habener J . A family of constitutive C/EBP-like DNA binding proteins attenuate the IL-1 alpha induced, NF kappa B mediated trans-activation of the angiotensinogen gene acute-phase response element. EMBO J. 1990; 9(12):3933-44. PMC: 552164. DOI: 10.1002/j.1460-2075.1990.tb07614.x. View

12.

Descombes P, Chojkier M, LICHTSTEINER S, Falvey E, Schibler U . LAP, a novel member of the C/EBP gene family, encodes a liver-enriched transcriptional activator protein. Genes Dev. 1990; 4(9):1541-51. DOI: 10.1101/gad.4.9.1541. View

13.

Baumann H, Jahreis G, Morella K . Interaction of cytokine- and glucocorticoid-response elements of acute-phase plasma protein genes. Importance of glucocorticoid receptor level and cell type for regulation of the elements from rat alpha 1-acid glycoprotein and beta-fibrinogen genes. J Biol Chem. 1990; 265(36):22275-81. View

14.

Isshiki H, Akira S, Sugita T, Nishio Y, Hashimoto S, Pawlowski T . Reciprocal expression of NF-IL6 and C/EBP in hepatocytes: possible involvement of NF-IL6 in acute phase protein gene expression. New Biol. 1991; 3(1):63-70. View

15.

Cao Z, Umek R, McKnight S . Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells. Genes Dev. 1991; 5(9):1538-52. DOI: 10.1101/gad.5.9.1538. View

16.

Williams S, Cantwell C, Johnson P . A family of C/EBP-related proteins capable of forming covalently linked leucine zipper dimers in vitro. Genes Dev. 1991; 5(9):1553-67. DOI: 10.1101/gad.5.9.1553. View

17.

Williams P, Ratajczak T, Lee S, Ringold G . AGP/EBP(LAP) expressed in rat hepatoma cells interacts with multiple promoter sites and is necessary for maximal glucocorticoid induction of the rat alpha-1 acid glycoprotein gene. Mol Cell Biol. 1991; 11(10):4959-65. PMC: 361476. DOI: 10.1128/mcb.11.10.4959-4965.1991. View

18.

Natsuka S, Isshiki H, Akira S, Kishimoto T . Augmentation of haptoglobin production in Hep3B cell line by a nuclear factor NF-IL6. FEBS Lett. 1991; 291(1):58-62. DOI: 10.1016/0014-5793(91)81103-f. View

19.

Bengal E, Ransone L, Scharfmann R, Dwarki V, Tapscott S, Weintraub H . Functional antagonism between c-Jun and MyoD proteins: a direct physical association. Cell. 1992; 68(3):507-19. DOI: 10.1016/0092-8674(92)90187-h. View

20.

Brechner T, Hocke G, Goel A, Fey G . Interleukin 6 response factor binds co-operatively at two adjacent sites in the promoter upstream region of the rat alpha 2-macroglobulin gene. Mol Biol Med. 1991; 8(2):267-85. View