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Glucocorticoid receptor interacting protein‐1 (GRIP‐1) is a novel transcriptional co‐activator for IRF‐1‐inducible genes
Author(s) -
Damera Gautam,
Gu Su,
Kassel Olivier,
Amrani Yassine,
Tliba Omar
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.718.1
Subject(s) - transfection , chromatin immunoprecipitation , reporter gene , activator (genetics) , glucocorticoid receptor , transactivation , microbiology and biotechnology , transcription factor , irf4 , promoter , chemistry , biology , receptor , gene , gene expression , glucocorticoid , endocrinology , biochemistry
IFN Regulatory Factor‐1 (IRF‐1) is an important transcription factor involved in the regulation of IFNs and TNFα‐inducible genes. GR‐interacting protein 1 (GRIP‐1) plays a critical role in the transcriptional regulation of glucocorticoid receptor (GR). Recent evidence showed that GRIP‐1 interacts and modulates IRF‐3‐dependent gene expression. We here examined whether manipulating the levels of such co‐factor modulates the transcriptional regulation of IRF‐1‐inducible genes. Airway smooth muscle (ASM) cells were co‐transfected with 2 μg constitutively active (CA)‐GRIP‐1 (kindly provided by Dr. Rogatsky) or pcDNA3 (used as a negative control) vectors and 2 μg of IRF‐1 reporter construct. After 48 h, cells were either left untreated or treated with TNFα (10 ng/ml) and IFNγ(1000 UI/ml) for 6 h. In parallel experiments, cells were co‐transfected with 2 μg CA‐GRα, 2 μg of CA‐GRIP‐1 or pcDNA3 vectors and 2 μg of IRF‐1 reporter construct. After 48 h, cells were treated as described above. We found that CA‐GRIP‐1 by itself dramatically enhanced IRF‐1 reporter activity in both basal and cytokine‐treated cells. Interestingly, overexpression of GRα inhibited IRF‐1 reporter activity in pcDNA3 transfected cells, an inhibition that was completely prevented in GRIP‐1‐overexpressing cells. Further, chromatin‐immunoprecipitation assay revealed a marked enrichment of GRIP‐1 on IRF‐1 DNA binding sites of CD38 promoter in cells‐treated with TNFα and IFNγ. Together, these data expand the role of GRIP‐1 from co‐activator restricted to nuclear receptors to include other transcription factors such as IRF‐1.