Differential regulation of glucocorticoid receptor transcriptional activation via AF-1-associated proteins.
The hormone-activated glucocorticoid receptor (GR), through its N- and C-terminal transcriptional activation functions AF-1 and AF-2, controls the transcription of target genes presumably through interaction(s) with transcriptional regulatory factors. Utilizing a modified yeast two-hybrid approach, we have identified the tumor susceptibility gene 101 (TSG101) and the vitamin D receptor-interacting protein 150 (DRIP150) as proteins that interact specifically with a functional GR AF-1 surface. In yeast and mammalian cells, TSG101 represses whereas DRIP150 enhances GR AF-1-mediated transactivation. Thus, GR AF-1 is capable of recruiting both positive and negative regulatory factors that differentially regulate GR transcriptional enhancement. In addition, we show that another member of the DRIP complex, DRIP205, interacts with the GR ligand binding domain in a hormone-dependent manner and facilitates GR transactivation in concert with DRIP150. These results suggest that DRIP150 and DRIP205 functionally link GR AF-1 and AF-2, and represent important mediators of GR transcriptional enhancement.
Hittelman
A B
AB
Department of Microbiology and the Kaplan Comprehensive Cancer Center, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Burakov
D
D
Iñiguez-Lluhí
J A
JA
Freedman
L P
LP
Garabedian
M J
MJ
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D000099177:Tsg101 Protein
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D005938:Glucocorticoids; D009687:Nuclear Proteins; D011965:Receptors, Glucocorticoid; D015534:Trans-Activators; D014157:Transcription Factors; D000099177:Tsg101 Protein; C117286:CRSP protein, human