Interaction of the tau2 transcriptional activation domain of glucocorticoid receptor with a novel steroid receptor coactivator, Hic-5, which localizes to both focal adhesions and the nuclear matrix.
Hic-5 (hydrogen peroxide-inducible clone-5) is a focal adhesion protein that is involved in cellular senescence. In the present study, a yeast two-hybrid screen identified Hic-5 as a protein that interacts with a region of the glucocorticoid receptor that includes a nuclear matrix-targeting signal and the tau2 transcriptional activation domain. In ... transiently transfected mammalian cells, overexpression of Hic-5 potentiated the activation of reporter genes by all steroid receptors, excluding the estrogen receptor. The activity of the estrogen receptor and the thyroid hormone receptor was stimulated by Hic-5 in the presence but not in the absence of coexpressed coactivator GRIP1. In biochemical fractionations and indirect immunofluorescence assays, a fraction of endogenous Hic-5 in REF-52 cells and transiently expressed Hic-5 in Cos-1 cells was associated with the nuclear matrix. The C-terminal region of Hic-5, which contains seven zinc fingers arranged in four LIM domains, was required for interaction with focal adhesions, the nuclear matrix, steroid receptors, and the tau2 domain of glucocorticoid receptor. The N-terminal region of Hic-5 possesses a transcriptional activation domain and was essential for the coactivator activity of Hic-5. Given the coexisting cytoplasmic and nuclear distributions of Hic-5 and its role in steroid receptor-mediated transcriptional activation, it is proposed that Hic-5 might transmit signals that emanate at cell attachment sites and regulate transcription factors, such as steroid receptors.
Mesh Terms:
Animals, Binding Sites, COS Cells, Cell Line, Cell Nucleus, Cercopithecus aethiops, Cytoplasm, Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Intracellular Signaling Peptides and Proteins, Mice, Nuclear Matrix, Receptors, Androgen, Receptors, Glucocorticoid, Receptors, Mineralocorticoid, Receptors, Progesterone, Transcriptional Activation, Zinc Fingers
Animals, Binding Sites, COS Cells, Cell Line, Cell Nucleus, Cercopithecus aethiops, Cytoplasm, Cytoskeletal Proteins, DNA-Binding Proteins, Humans, Intracellular Signaling Peptides and Proteins, Mice, Nuclear Matrix, Receptors, Androgen, Receptors, Glucocorticoid, Receptors, Mineralocorticoid, Receptors, Progesterone, Transcriptional Activation, Zinc Fingers
Mol. Biol. Cell
Date: Jun. 01, 2000
PubMed ID: 10848625
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