The glucocorticoid receptor interacting protein 1 (GRIP1) localizes in discrete nuclear foci that associate with ND10 bodies and are enriched in components of the 26S proteasome.
The glucocorticoid receptor interacting protein-1 (GRIP1) is a member of the steroid receptor coactivator (SRC) family of transcriptional regulators. Green fluorescent protein (GFP) fusions were made to full-length GRIP1, and a series of GRIP1 mutants lacking the defined regulatory regions and the intracellular distribution of these proteins was studied in HeLa cells. The distribution of GRIP1 was complex, ranging from diffuse nucleoplasmic to discrete intranuclear foci. Formation of these foci was dependent on the C-terminal region of GRIP1, which contains the two characterized transcriptional activation domains, AD1 and AD2. A subpopulation of GRIP1 foci associate with ND10s, small nuclear bodies that contain several proteins including PML, SP100, DAXX, and CREB-binding protein (CBP). Association with the ND10s is dependent on the AD1 of GRIP1, a region of the protein previously described as a CBP-interacting domain. The GRIP1 foci are enriched in components of the 26S proteasome, including the core 20S proteasome, PA28alpha, and ubiquitin. In addition, the irreversible proteasome inhibitor lactacystin induced an increase in the total fluorescence intensity of the GFP-GRIP1 expressing cells, demonstrating that GRIP1 is degraded by the proteasome. These findings suggest the intriguing possibility that degradation of GRIP1 by the 26S proteasome may be a key component of its regulation.
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health Bethesda, Maryland 20892-5055, USA.
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Baumann
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Wolford
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Reyes
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Maruvada
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Lim
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Yen
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Stallcup
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Hager
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D034961:Antigens, Nuclear; D001324:Autoantigens / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D050882:CREB-Binding Protein; D002352:Carrier Proteins / Q000378:metabolism; D022003:Cell Nucleus Structures / Q000378:metabolism*; D056970:Co-Repressor Proteins; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D034961:Antigens, Nuclear; D001324:Autoantigens; D002352:Carrier Proteins; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D018832:Molecular Chaperones; C498001:NCOA2 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D000071156:Promyelocytic Leukemia Protein; D011480:Protease Inhibitors; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014452:Ubiquitins; C067713:lactacystin; C066642:SP100 protein, human; C070576:PML protein, human; D049452:Green Fluorescent Proteins; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D056921:Nuclear Receptor Coactivator 3; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D000111:Acetylcysteine