| Structural highlights
Function
[PRGR_HUMAN] The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.[1] [2] [3] [4] [5] [6] [7] Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation.[8] [9] [10] [11] [12] [13] [14]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The DNA binding domain (DBD) of nuclear hormone receptors contains a highly conserved globular domain and a less conserved carboxyl-terminal extension (CTE). Despite previous observations that the CTEs of some classes of nuclear receptors are structured and interact with DNA outside of the hexanucleotide hormone response element (HRE), there has been no evidence for such a CTE among the steroid receptors. We have determined the structure of the progesterone receptor (PR)-DBD-CTE DNA complex at a resolution of 2.5 A, which revealed binding of the CTE to the minor groove flanking the HREs. Alanine substitutions of the interacting CTE residues reduced affinity for inverted repeat HREs separated by three nucleotides, and essentially abrogated binding to a single HRE. A highly compressed minor groove of the trinucleotide spacer and a novel dimerization interface were also observed. A PR binding site selection experiment revealed sequence preferences in the trinucleotide spacer and flanking DNA. These results, taken together, support the notion that sequences outside of the HREs influence the DNA binding affinity and specificity of steroid receptors.
Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements.,Roemer SC, Donham DC, Sherman L, Pon VH, Edwards DP, Churchill ME Mol Endocrinol. 2006 Dec;20(12):3042-52. Epub 2006 Aug 24. PMID:16931575[15]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pierson-Mullany LK, Lange CA. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. PMID:15572662 doi:10.1128/MCB.24.24.10542-10557.2004
- ↑ Narayanan R, Edwards DP, Weigel NL. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. PMID:15798179 doi:25/8/2885
- ↑ Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. PMID:17020914 doi:gkl691
- ↑ Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. PMID:17347654 doi:7601602
- ↑ Daniel AR, Faivre EJ, Lange CA. Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. PMID:17717077 doi:me.2007-0248
- ↑ Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. PMID:17173941 doi:S0039-128X(06)00225-X
- ↑ Faivre EJ, Daniel AR, Hillard CJ, Lange CA. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. Epub 2008 Jan 17. PMID:18202149 doi:me.2007-0437
- ↑ Pierson-Mullany LK, Lange CA. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. PMID:15572662 doi:10.1128/MCB.24.24.10542-10557.2004
- ↑ Narayanan R, Edwards DP, Weigel NL. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. PMID:15798179 doi:25/8/2885
- ↑ Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. PMID:17020914 doi:gkl691
- ↑ Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. PMID:17347654 doi:7601602
- ↑ Daniel AR, Faivre EJ, Lange CA. Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. PMID:17717077 doi:me.2007-0248
- ↑ Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. PMID:17173941 doi:S0039-128X(06)00225-X
- ↑ Faivre EJ, Daniel AR, Hillard CJ, Lange CA. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. Epub 2008 Jan 17. PMID:18202149 doi:me.2007-0437
- ↑ Roemer SC, Donham DC, Sherman L, Pon VH, Edwards DP, Churchill ME. Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements. Mol Endocrinol. 2006 Dec;20(12):3042-52. Epub 2006 Aug 24. PMID:16931575 doi:http://dx.doi.org/10.1210/me.2005-0511
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