Protein-DNA Interactions at Steroid Hormone Regulated Genes

Scheidereit, Claus; Ahe, Dietmar von der; Cato, Andrew C. B.; Wenz, Michael; Suske, Guntram; Carlson, Christopher; Bosshard, Heinz E.; Westphal, Hannes M.; Beato, Miguel

doi:10.3109/07435808909036347

Cited by 16 publications

(11 citation statements)

References 26 publications

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“…Actinomycin D inhibition studies show that the effect of glucocorticoids is at the transcriptional level. The human IκBα promoter carries the motif G GACGAAGCCA G TT C T at positions −93 to −73 which contains the conserved hexanucleotide motif A/TGTTCT (underlined) and three of the four contact residues (in bold) for GR binding to DNA (Beato, 1989; Scheidereit et al ., 1989). This receptor binding motif is possibly responsible for the glucocorticoid response of the IκBα promoter in HeLa cells.…”

Section: Discussionmentioning

confidence: 99%

Ikappa Balpha -independent downregulation of NF-kappa B activity by glucocorticoid receptor

Heck

Bender²,

Kullmann³

et al. 1997

The EMBO Journal

278

147

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IκBα is an inhibitor protein that prevents nuclear transport and activation of the transcription factor NF‐κB. In acute inflammation, NF‐κB is activated and increases the expression of several pro‐inflammatory cytokine and chemokine genes. Glucocorticoids counteract this process. It has been proposed that the glucocorticoid‐dependent inhibition of NF‐κB activity is mediated by increased synthesis of IκBα which should then sequester NF‐κB in an inactive cytoplasmic form. Here, we show by the use of a mutant glucocorticoid receptor and steroidal ligands that hormone‐induced IκBα synthesis and inhibition of NF‐κB activity are separable biochemical processes. A dimerization‐defective glucocorticoid receptor mutant that does not enhance the IκBα level is still able to repress NF‐κB activity. Conversely, glucocorticoid analogues competent in enhancing IκBα synthesis do not repress NF‐κB activity. These results demonstrate that increased synthesis of IκBα is neither required nor sufficient for the hormone‐mediated downmodulation of NF‐κB activity.

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Section: Discussionmentioning

confidence: 99%

Ikappa Balpha -independent downregulation of NF-kappa B activity by glucocorticoid receptor

Heck

Bender²,

Kullmann³

et al. 1997

The EMBO Journal

278

147

View full text Add to dashboard Cite

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“…Likewise, the human betaretrovirus appears to be preferentially located in lymphoid tissues with a limited viral abundance in the liver, where the end organ damage occurs in patients with PBC. The biology of MMTV infection may also explain the female preponderance seen in patients with PBC as viral replication is regulated in part by a progesterone responsive glucocorticoid regulatory element in the promoter region of the MMTV LTR (29,30).…”

Section: Discussionmentioning

confidence: 99%

Does a betaretrovirus infection trigger primary biliary cirrhosis?

Shen

Guo

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

217

246

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Patients with primary biliary cirrhosis develop progressive ductopenia associated with the production of antimitochondrial antibodies that react with a protein aberrantly expressed on biliary epithelial cells and peri-hepatic lymph nodes. Although no specific microbe has been identified, it is thought that an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. Previous serologic studies have provided evidence to suggest a viral association with primary biliary cirrhosis. Here we describe the identification of viral particles in biliary epithelium by electron microscopy and the cloning of exogenous retroviral nucleotide sequences from patients with primary biliary cirrhosis. The putative agent is referred to as the human betaretrovirus because it shares close homology with the murine mammary tumor virus and a human retrovirus cloned from breast cancer tissue. In vivo, we have found that the majority of patients with primary biliary cirrhosis have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes. Moreover, the viral proteins colocalize to cells demonstrating aberrant autoantigen expression. In vitro, we have found that lymph node homogenates from patients with primary biliary cirrhosis can induce autoantigen expression in normal biliary epithelial cells in coculture. Normal biliary epithelial cells also develop the phenotypic manifestation of primary biliary cirrhosis when cocultivated in serial passage with supernatants containing the human betaretrovirus or the murine mammary tumor virus, providing a model to test Koch's postulates in vitro.

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“…In this respect, the observation of an association of more potent immunosuppressive therapy following transplant and earlier and more aggressive recurrence of PBC [147] is also of interest. MMTV replication is regulated in part by a progesterone-responsive glucocorticoid regulatory element in the promoter region, offering an alternative explanation for the female preponderance seen with PBC [148].…”

Section: Infectionsmentioning

confidence: 99%