Hormone-Dependent Interaction between the Amino- and Carboxyl-Terminal Domains of Progesterone Receptor in Vitro and in Vivo

Tetel, Marc J.

doi:10.1210/me.13.6.910

Cited by 89 publications

(108 citation statements)

References 42 publications

(91 reference statements)

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…Recently, it was found that the ERa N/C interaction was required for SRC-1-mediated synergism between AF-1 and AF-2 function [8,53]. The progesterone receptor (PR) showed direct N/C interaction in the presence of agonist R5020, but not in the presence of antagonist RU486 [54]. LxxLL motifs in the PR-B form were most probably not involved, because the shorter PR-A form, lacking these motifs, also showed N/C interaction [55].…”

Section: Discussionmentioning

confidence: 99%

Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Steketee

Berrevoets

Dubbink

et al. 2002

European Journal of Biochemistry

View full text Add to dashboard Cite

The N-terminal domain (NTD) and the ligand-binding domain (LBD) of the androgen receptor (AR) exhibit a ligand-dependent interaction (N/C interaction). Amino acids 3-36 in the NTD (AR 3)36 ) play a dominant role in this interaction. Previously, it has been shown that a FxxFF motif in AR 3)36 , 23 FxxLF 27 , is essential for LBD interaction. We demonstrate in the current study that AR 3)36 can be subdivided into two functionally distinct fragments: AR 3)13 and AR 16)36 . AR 3)13 does not directly interact with the AR LBD, but rather contributes to the transactivation function of the AR.NTD-AR.LBD complex. AR 16)36, encompassing the 23 FxxLF 27 motif, is predicted to fold into a long amphipathic a-helix. A second FxxFF candidate protein interaction motif within the helical structure, 30 VREVI 34 , shows no affinity to the LBD. Within AR 16)36 , amino acid residues in and flanking the 23 FxxLF 27 motif are demonstrated to modulate N/C interaction. Substitution of Q24 and N25 by alanine residues enhances N/C interaction. Substitution of amino acids flanking the 23 FxxLF 27 motif by alanines are inhibitory to LBD interaction.

show abstract

Section: Discussionmentioning

confidence: 99%

Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Steketee

Berrevoets

Dubbink

et al. 2002

European Journal of Biochemistry

View full text Add to dashboard Cite

show abstract

“…Analysis of the expression of potential mediators of ovulation in PRKO mice has demonstrated that LH-induced regulation of Cox-2, an enzyme that catalyses the production of prostaglandins and is essential for ovulation, is unaffected (Robker et al 2000). In contrast, the expression of two metalloproteinases, ADAMTS-1 (a desintegrin and metalloproteinase with thrombospondin motifs) and cathepsin-L (a lysosomal cysteine protease) is inhibited in mural granulosa cells of the mature follicle (Tetel et al 1999, Robker et al 2000 in PRKO mice. One of these proteases, ADAMTS-1, is essential for ovulation (Robker et al 2000) suggesting that this protein may represent a critical mediator of the progesterone-induced ovulatory event.…”

Section: Prs and Ovarian Functionmentioning

confidence: 99%

“…The production of these two isoforms is conserved in a number of vertebrate species including humans and rodents (Lessey et al 1983, Conneely et al 1989, Shyamala et al 1990, Giangrande & McDonnell 1999 and the ratios of the individual isoforms vary in reproductive tissues as a consequence of developmental (Shyamala et al 1990) and hormonal (Duffy et al 1997) status and during carcinogenesis (Graham et al 1996).…”

mentioning

confidence: 99%

“…Specifically, PR-B has been shown to function as a strong activator of transcription of several PR-dependent promoters and in a variety of cell types in which PR-A is inactive. In addition, when the PR-A and PR-B proteins are co-expressed in cultured cells, the PR-A can repress the activity of PR-B as well as the activity of other nuclear receptors (Giangrande & McDonnell 1999). Further, the PR-A and PR-B proteins also respond differently to progesterone antagonists (reviewed in Giangrande & McDonnell 1999).…”

mentioning

confidence: 99%

“…In addition, when the PR-A and PR-B proteins are co-expressed in cultured cells, the PR-A can repress the activity of PR-B as well as the activity of other nuclear receptors (Giangrande & McDonnell 1999). Further, the PR-A and PR-B proteins also respond differently to progesterone antagonists (reviewed in Giangrande & McDonnell 1999). While antagonist bound PR-A is inactive, antagonist bound PR-B can be converted to a strongly active transcription factor.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Reproductive tissue selective actions of progesterone receptors

Mulac‐Jeričević¹,

Conneely²

2004

Reproduction

231

118

View full text Add to dashboard Cite

The steroid hormone, progesterone, plays a central coordinate role in diverse events associated with female reproduction. In humans and other vertebrates, the biological activity of progesterone is mediated by modulation of the transcriptional activity of two progesterone receptors, PR-A and PR-B. These receptors arise from the same gene and exhibit both overlapping and distinct transcriptional activities in vitro. To delineate the individual roles of PR-A and PR-B in vivo, we have generated mouse models in which expression of a single PR isoform has been ablated. Analysis of the reproductive phenotypes of these mice has indicated that PR-A and PR-B mediate mostly distinct but partially overlapping reproductive responses to progesterone. While selective ablation of the PR-A protein (PR-A knockout mice, PRAKO mice) shows normal mammary gland response to progesterone but severe uterine hyperplasia and ovarian abnormalities, ablation of PR-B protein (PRBKO mice) does not affect biological responses of the ovary or uterus to progesterone but results in reduced pregnancy-associated mammary gland morphogenesis. The distinct tissue-specific reproductive responses to progesterone exhibited by these isoforms are due to regulation of distinct subsets of progesterone-dependent target genes by the individual PR isoforms. This review will summarize our current understanding of the selective contribution of PR isoforms to the cellular and molecular actions of progesterone in reproductive tissues.

show abstract

DNA‐binding properties of Drosophila ecdysone receptor isoforms and their modification by the heterodimerization partner ultraspiracle

Braun

Azoitei

Spindler-Barth

2009

Arch Insect Biochem Physiol

View full text Add to dashboard Cite

Transcriptional activity of ecdysone receptor (EcR) isoforms varies considerably and is modified further by the heterodimerization partner and hormone treatment. To investigate whether differences in DNA binding of receptor complexes are responsible for these variations in transcriptional activity, interaction of Drosophila EcR isoforms, and variants of Ultraspiracle (Usp), the orthologue of RXR, with the ecdysone response elements (EcRE) hsp 27, PAL-1, and DR-1, were determined by electrophoretic mobility shift assays. Receptor proteins were expressed in vertebrate cells (CHO-K1) in order to rule out an influence of endogenous receptor proteins. In the absence of a heterodimerization partner, weak DNA binding of EcR was detected even without hormone with EcR-A and -B1, but not EcR-B2. In the presence of hormone, all three isoforms show increased binding to the hsp 27 EcRE. The heterodimerization partner Usp increased DNA binding considerably. The hormone effect of heterodimers is more pronounced with both EcR-B isoforms compared to EcR-A. Two specific bands were obtained for EcR-A and B1 but only one band is visible with EcR-B2. Deletion of the C-domain of Usp still allows basal DNA binding of the heterodimer, but in contrast to full-length Usp, addition of hormone decreases the intensity of the retarded receptor band of all EcR isoforms and the EcREs hsp27 and DR-1 considerably, whereas interaction with the EcRE PAL-1 is only slightly affected. Synergistic effects on transcriptional activity are associated with the formation of different receptor DNA-complexes observed with 1xhsp27 and 3xhsp27. Comparison of DNA-binding properties of EcR isoforms and EcR/Usp heterodimers revealed that binding of receptor complexes to hsp 27 EcRE is dependent on the AB domain of EcR and the AB-, C-, and D-domains of the heterodimerization partner. Interaction with the hsp 27 EcRE correlates neither with ligand binding nor with transcriptional activity of the various receptor complexes. We, therefore, conclude that the different receptor functions are regulated separately, for example, by interaction with co-modulators or post-transcriptional modifications.

show abstract

Hormone-Dependent Interaction between the Amino- and Carboxyl-Terminal Domains of Progesterone Receptor in Vitro and in Vivo

Cited by 89 publications

References 42 publications

Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Reproductive tissue selective actions of progesterone receptors

DNA‐binding properties of Drosophila ecdysone receptor isoforms and their modification by the heterodimerization partner ultraspiracle

Contact Info

Product

Resources

About

Hormone-Dependent Interaction between the Amino- and Carboxyl-Terminal Domains of Progesterone Receptor in Vitro and in Vivo

Cited by 89 publications

References 42 publications

Amino acids 3–13 and amino acids in and flanking the 23FxxLF27 motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Amino acids 3–13 and amino acids in and flanking the 23FxxLF27 motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Reproductive tissue selective actions of progesterone receptors

DNA‐binding properties of Drosophila ecdysone receptor isoforms and their modification by the heterodimerization partner ultraspiracle

Contact Info

Product

Resources

About

Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor

Amino acids 3–13 and amino acids in and flanking the ²³FxxLF²⁷ motif modulate the interaction between the N‐terminal and ligand‐binding domain of the androgen receptor