An additional region of coactivator GRIP1 required for interaction with the hormone-binding domains of a subset of nuclear receptors
- PMID: 9920895
- DOI: 10.1074/jbc.274.6.3496
An additional region of coactivator GRIP1 required for interaction with the hormone-binding domains of a subset of nuclear receptors
Abstract
Transcriptional coactivators of the p160 family (SRC-1, GRIP1, and p/CIP) associate with DNA-bound nuclear receptors (NRs) and help the NRs to recruit an active transcription initiation complex to the promoters of target genes. Previous studies have demonstrated the importance of the NR interaction domain (NID) of p160 proteins containing three NR box motifs (LXXLL) for the interaction with the hormone-binding domains of NRs. Here we report that, in addition to NID, another region of coactivator GRIP1 (amino acids 1011-1121), called the auxiliary NID (NIDaux), is required in vitro and in vivo for efficient interaction with a subset of NRs, including the glucocorticoid receptor (GR), androgen receptor, and retinoic acid receptor alpha. A second group of NRs, which includes the progesterone receptor, retinoid X receptor alpha, thyroid hormone receptor beta1, and vitamin D receptor, required only NID for efficient interaction. For binding to GR, the NID and NIDaux of GRIP1 must act in cis, but deletion of up to 144 amino acids between the two regions did not reduce binding efficiency. Amino acids 1011-1121 of GRIP1 also contain a p300 interaction domain, but mutational analysis indicated that the p300 interaction function within this region is separable from the ability to contribute to GR hormone-binding domain binding. SRC-1 lacks an NIDaux activity equivalent to that in GRIP1.
Similar articles
-
The roles of protein-protein interactions and protein methylation in transcriptional activation by nuclear receptors and their coactivators.J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):139-45. doi: 10.1016/s0960-0760(03)00222-x. J Steroid Biochem Mol Biol. 2003. PMID: 12943698 Review.
-
The SRC family of nuclear receptor coactivators.Gene. 2000 Mar 7;245(1):1-11. doi: 10.1016/s0378-1119(00)00024-x. Gene. 2000. PMID: 10713439 Review.
-
Multiple signal input and output domains of the 160-kilodalton nuclear receptor coactivator proteins.Mol Cell Biol. 1999 Sep;19(9):6164-73. doi: 10.1128/MCB.19.9.6164. Mol Cell Biol. 1999. PMID: 10454563 Free PMC article.
-
Nuclear receptor-binding sites of coactivators glucocorticoid receptor interacting protein 1 (GRIP1) and steroid receptor coactivator 1 (SRC-1): multiple motifs with different binding specificities.Mol Endocrinol. 1998 Feb;12(2):302-13. doi: 10.1210/mend.12.2.0065. Mol Endocrinol. 1998. PMID: 9482670
-
GRIP1, a transcriptional coactivator for the AF-2 transactivation domain of steroid, thyroid, retinoid, and vitamin D receptors.Mol Cell Biol. 1997 May;17(5):2735-44. doi: 10.1128/MCB.17.5.2735. Mol Cell Biol. 1997. PMID: 9111344 Free PMC article.
Cited by
-
Multifaceted Transcriptional Network of Estrogen-Related Receptor Alpha in Health and Disease.Int J Mol Sci. 2023 Feb 21;24(5):4265. doi: 10.3390/ijms24054265. Int J Mol Sci. 2023. PMID: 36901694 Free PMC article. Review.
-
Decreased 11β-hydroxysteroid dehydrogenase 1 in lungs of steroid receptor coactivator (Src)-1/-2 double-deficient fetal mice is caused by impaired glucocorticoid and cytokine signaling.FASEB J. 2020 Dec;34(12):16243-16261. doi: 10.1096/fj.202001809R. Epub 2020 Oct 18. FASEB J. 2020. PMID: 33070362 Free PMC article.
-
Crosstalk in inflammation: the interplay of glucocorticoid receptor-based mechanisms and kinases and phosphatases.Endocr Rev. 2009 Dec;30(7):830-82. doi: 10.1210/er.2009-0013. Epub 2009 Nov 4. Endocr Rev. 2009. PMID: 19890091 Free PMC article. Review.
-
The p160 coactivator PAS-B motif stabilizes nuclear receptor binding and contributes to isoform-specific regulation by thyroid hormone receptors.J Biol Chem. 2009 Jul 17;284(29):19554-63. doi: 10.1074/jbc.M109.007542. Epub 2009 Jun 1. J Biol Chem. 2009. PMID: 19487700 Free PMC article.
-
Kinetic and thermodynamic characterization of dihydrotestosterone-induced conformational perturbations in androgen receptor ligand-binding domain.Mol Endocrinol. 2009 Aug;23(8):1231-41. doi: 10.1210/me.2008-0304. Epub 2009 May 14. Mol Endocrinol. 2009. PMID: 19443608 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous