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- Title
STAT3/NFκB Interplay in the Regulation of α2-Macroglobulin Gene Expression During Rat Liver Development and the Acute Phase Response.
- Authors
UskokoviĆ, Aleksandra; DiniĆ, Svetlana; MihailoviĆ, Mirjana; Grigorov, Ilijana; IvanoviĆ-MatiĆ, Svetlana; BogojeviĆ, Desanka; GrdoviĆ, Nevena; ArambašiĆ, Jelena; VidakoviĆ, Melita; MartinoviĆ, Vesna; PetroviĆ, Miodrag; PoznanoviĆ, Goran
- Abstract
The synthesis of alpha-2-macroglobulin (α2M) is low in adult rat liver and elevated in fetal liver. During the acute-phase (AP) response it becomes significantly increased in both adult and fetal liver. In this work, the cross talk of STAT3 and NF-κB transcription factors during α2M gene expression was analysed. Using immunoblotting, their cellular compartmentalization was examined by comparing the cytoplasmic levels of STAT3 and NF-κB with their active equivalents, the 86 and 91 kDa isoforms and p65-subunit, respectively, in the nuclear extract and nuclear matrix. Different partitioning dynamics of the transcription factors were observed. At the level of protein-DNA interactions, studied by α2M promoter affinity chromatography, it was established that different ratios of promoter-binding STAT3 isoforms participated in elevated hepatic transcription in the basal state fetus and the AP-adult, but only the 91 kDa isoform in the AP-fetus. Unchanged levels of DNA-bound p65 in the control and AP-fetus suggest that it participated in constitutive transcription. The promoter-binding of p65 observed in the AP-adult suggests that it was involved in transcriptional stimulation of α2M expression. The selective enrichment of the AP-adult nuclear matrix with promoter-binding STAT3 disclosed the importance of this association in the induction of transcription. Protein-protein interactions were examined by co-immunoprecipitation. Interactions between the 86 kDa STAT3 isoform and p65 that were observed in the control and AP-fetus and of both the 86 and 91 kDa STAT3 isoforms with p65 in the AP-adult, suggest that protein-protein interactions were functionally connected to increased transcription. We concluded that α2M gene expression is driven by developmental- and AP-related mechanisms that rely on STAT3/NF-κB interplay. IUBMB Life, 59: 170-178, 2007
- Subjects
ALPHA macroglobulins; MACROGLOBULINS; BLOOD proteins; GLOBULINS; LABORATORY rats; NUCLEAR matrix; CELL nuclei; NONHISTONE chromosomal proteins
- Publication
IUBMB Life, 2007, Vol 59, Issue 3, p170
- ISSN
1521-6543
- Publication type
Article
- DOI
10.1080/15216540701272612