Specific binding of progesterone receptor to progesterone‐responsive elements does not require prior dimerization

Cohen‐Solal, Karine; Bailly, Alain; Rauch, Claudine; Quesne, Monique; Milgröm, Edwin

doi:10.1111/j.1432-1033.1993.tb17912.x

Cited by 14 publications

(10 citation statements)

References 42 publications

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“…It was concluded from this study with rabbit PR that the LBD was required for homodimerization and that the amino terminus was not involved (12). The reason for the apparent discrepancy between the results with rabbit PR (12) and our present findings is not known. One possibility is the use of different methodologies to analyze PR-PR interactions.…”

Section: Discussioncontrasting

confidence: 93%

Hinge and Amino-Terminal Sequences Contribute to Solution Dimerization of Human Progesterone Receptor

Tetel

Jung

Carbajo

et al. 1997

Molecular Endocrinology

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We and others have shown previously that progesterone receptors (PR) form homodimers in solution in the absence of DNA and that dimers are the preferential form of receptor that binds with high affinity to target DNA. To determine the sequence regions involved in solution homodimerization, wild type PR and truncated PR proteins were expressed in an insect baculovirus system. The expression constructs included the ligand-binding domain [LBD, amino acids (aa) 688-933], the LBD plus hinge (hLBD, aa 634-933), the hLBD plus the DNA-binding domain (DhLBD, aa 538-933), and the full- length A and B isoforms of PR. PR-PR interactions were detected by three methods, coimmunoprecipitation of the PR fragments with full-length PR-A, pull-down of PR-polypeptides with polyhistidine-tagged versions of the same polypeptides immobilized to metal affinity columns and cooperative ligand-binding assays (Hill coefficient, n(H) > 1 indicating PR-PR interaction). By all three assays, the LBD alone was not sufficient to mediate protein-protein interaction. However, the LBD did exhibit other properties ascribed to this domain, including binding to steroids with a relatively good affinity and specificity, ligand-induced conformational changes at the carboxyl terminus tail and binding of heat shock protein 90 and its dissociation in response to hormone. Thus, failure of the expressed LBD to mediate dimerization does not appear to be due to an extensively misfolded or unstable polypeptide. The minimal carboxyl-terminal fragment capable of mediating PR-PR interaction was the hLBD construct. However, by immobilized metal affinity chromatography assay, self-association of PR-A was 3.5-fold more efficient than that of either the DhLBD or hLBD constructs. An expressed amino-terminal domain (aa 165-535) lacking the DNA-binding domain, hinge, and LBD was found to physically associate with PR-A or with another amino-terminal fragment lacking the LBD, but retaining the DNA-binding domain. These results provide evidence for direct amino-terminal interactions in the more efficient PR-PR interaction exhibited by wild-type PR-A, as compared with DhLBD and hLBD constructs. The overall results of this paper are consistent with the conclusion that the carboxyl-terminal LBD is not sufficient for mediating PR dimerization and that multiple regions, including the hinge and amino-terminal sequences, contribute either directly or indirectly to homodimerization of PR.

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Section: Discussioncontrasting

confidence: 93%

Hinge and Amino-Terminal Sequences Contribute to Solution Dimerization of Human Progesterone Receptor

Tetel

Jung

Carbajo

et al. 1997

Molecular Endocrinology

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“…To our knowledge, P4 is a lipid soluble hormone which can easily pass across membrane cell and its effects are mediated through PgR in the cytoplasm then receptors dimerization take place and these complexes enter to the nucleus and bind to PRE region in promoter target genes [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

The effect of progesterone and 17-β estradiol on membrane-bound HLA-G in adipose derived stem cells

Moslehi

Hashemibeni

Moslehi

et al. 2016

Korean J Physiol Pharmacol

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Membrane-bound HLA-G (mHLA-G) discovery on adipose derived stem cells (ADSCs) as a tolerogenic and immunosuppressive molecule was very important. Many documents have shown that HLA-G expression can be controlled via some hormones such as progesterone (P4) and estradiol (E2). Therefore, this study was designed to evaluate progesterone and estradiol effects on mHLA-G in ADSCs at restricted and combination concentrations. Three independent cell lines were cultured in complete free phenol red DMEM and subcultured to achieve suffi cient cells. These cells were treated with P4, E2 and P4 plus E2 at physiologic and pregnancy concentrations for 3 days in cell culture conditions. The HLA-G positive ADSCs was measured via monoclonal anti HLA-G-FITC/MEMG-09 by means of flow cytometry in nine groups. Data were analyzed by one way ANOVA and Tukey's post hoc tests. There were no signifi cant values of the mean percentage of HLA-G positive cells in E2-treated and the combination of P4 plus E2-treated ADSCs compared to control cells (p value>0.05) but P4 had a signifi cant increase on mHLA-G in ADSCs (p value<0.05). High P4 concentration increased mHLA-G but E2 and the combination of P4 plus E2 could not change mHLA-G on ADSCs.

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“…In the classical pathway, upon ligand binding, cytoplasmic PR translocates to the nucleus and triggers expression of genes with the PRE (progesterone response element) sequence [11]. PR takes part in a large number of alternative, non-genomic signalling cascades in which PR activates MAPK and PI3K/AKT pathways rapidly initiating various cellular events (e.g.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast growth factor signalling induces loss of progesterone receptor in breast cancer cells

et al. 2016

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We have recently demonstrated that, fibroblast growth factor 2 (FGFR2), signalling via ribosomal S6 kinase 2 (RSK2), promotes progression of breast cancer (BCa). Loss of progesterone receptor (PR), whose activity in BCa cells can be stimulated by growth factor receptors (GFRs), is associated with poor patient outcome. Here we showed that FGF7/FGFR2 triggered phosphorylation of PR at Ser294, PR ubiquitination and subsequent receptor`s degradation via the 26S proteasome pathway in BCa cells. We further demonstrated that RSK2 mediated FGF7/FGFR2-induced PR downregulation. In addition, a strong synergistic effect of FGF7 and progesterone (Pg), reflected in the enhanced anchorage-independent growth and cell migration, was observed. Analysis of clinical material demonstrated that expression of PR inversely correlated with activated RSK (RSK-P) (p = 0.016). Patients with RSK-P(+)/PR(–) tumours had 3.629-fold higher risk of recurrence (p = 0.002), when compared with the rest of the cohort. Moreover, RSK-P(+)/PR(–) phenotype was shown as an independent prognostic factor (p = 0.006). These results indicate that the FGF7/FGFR2-RSK2 axis promotes PR turnover and activity, which may sensitize BCa cells to stromal stimuli and contribute to the progression toward steroid hormone negative BCa.

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Specific binding of progesterone receptor to progesterone‐responsive elements does not require prior dimerization

Cited by 14 publications

References 42 publications

Hinge and Amino-Terminal Sequences Contribute to Solution Dimerization of Human Progesterone Receptor

Hinge and Amino-Terminal Sequences Contribute to Solution Dimerization of Human Progesterone Receptor

The effect of progesterone and 17-β estradiol on membrane-bound HLA-G in adipose derived stem cells

Fibroblast growth factor signalling induces loss of progesterone receptor in breast cancer cells

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