Association of the glucocorticoid receptor with STAT3, C/EBPβ, and the hormone-responsive element within the rat haptoglobin gene promoter during the acute phase response
2010
Аутори:
Arambašić Jovanović, JelenaPoznanović, Goran
Ivanović-Matić, Svetlana
Bogojević, Desanka
Mihailović, Mirjana
Uskoković, Aleksandra
Grigorov, Ilijana
Тип документа:
Чланак у часопису (Објављена верзија)
,
© 2010 International Union of Biochemistry and Molecular Biology, Inc.
Метаподаци
Приказ свих података о документуАпстракт:
Upregulation of haptoglobin (Hp) expression in the rat during the acute phase (AP) response is the result of synergistic effects of IL-6–, IL-1β–, and corticosterone-activated signaling pathways. IL-6 signaling terminates in cis–trans interactions of the Hp gene hormone-responsive element (HRE) with transcription factors STAT3 and C/EBPβ. The aim of this study was to examine the unresolved molecular mechanism of glucocorticoid action. A 3-fold rise in serum corticosterone at 2 and 4 h of the AP response induced by turpentine administration preceded a 2.3-fold increase in the rate of Hp gene transcription at 12 h that was accompanied by a 4.8-fold increase in glucocorticoid receptor (GR), the appearance of an 86-kDa STAT3 isoform and 3.9-, 1.9-, and 1.7-fold increased amounts of 91-kDa STAT3, 35- and 42-kDa C/EBPβ isoforms in the nucleus. These events resulted in 4.6- and 2.5-fold increased Hp levels in the liver and serum at 24 h. HRE affinity chromatography and immunoblot analysis revealed that maximal occupancy of the HRE with GR, STAT3, and C/EBPβ at 12 h correlated with increased transcriptional activity of the Hp gene. Coimmunoprecipitation experiments showed that activated GR established de novo interaction with STAT3 isoforms while GR–C/EBPβ interactions observed during basal transcription increased during the AP response. Computer analysis of the HRE disclosed two potential GR-binding sites: one overlapping STAT3, another adjacent to a C/EBPβ-binding site. This finding and the experimental results suggest that activated GR through direct interactions with STAT3 and C/EBPβ, participates in Hp gene upregulation as a transcriptional coactivator.
Извор:
IUBMB Life, 2010, 62, 3, 227-236
DOI: 10.1002/iub.313
ISSN: 1521-6543
PubMed: 20155810