Abstract
Tumor susceptibility gene 101 (TSG101) is involved in endosomal maturation and has been implicated in the transcriptional regulation of several steroid hormone receptors, although a detailed characterization of such regulation has yet to be conducted. Here we directly measure binding of TSG101 to one steroid hormone receptor, the glucocorticoid receptor (GR). Using biophysical and cellular assays, we show that the coiled-coil domain of TSG101 (1) binds and folds the disordered N-terminal domain of the GR, (2) upon binding improves the DNA binding of the GR in vitro, and (3) enhances the transcriptional activity of the GR in vivo. Our findings suggest that TSG101 is a bona fide transcriptional co-regulator of the GR and reveal how the underlying thermodynamics affect the function of the GR.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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DNA-Binding Proteins / physiology*
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Endosomal Sorting Complexes Required for Transport / genetics
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Endosomal Sorting Complexes Required for Transport / metabolism*
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Endosomal Sorting Complexes Required for Transport / physiology*
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Endosomes / metabolism
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Gene Expression Regulation / genetics
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Gene Expression Regulation / physiology
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HeLa Cells
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Humans
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Protein Binding
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Protein Domains / physiology
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Receptors, Glucocorticoid / metabolism*
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Regulatory Elements, Transcriptional / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription Factors / physiology*
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Transcription, Genetic / genetics
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Transcriptional Activation / genetics
Substances
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DNA-Binding Proteins
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Endosomal Sorting Complexes Required for Transport
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Receptors, Glucocorticoid
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Transcription Factors
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Tsg101 protein