A barley cDNA clone with homology to the DNA-binding domain of the steroid hormone receptors

Abstract The N-terminal domains (NTDs) of many members of the nuclear hormone receptor (NHR) family contain potent transcription-activating functions (AFs). Knowledge of the mechanisms of action of the NTD AFs has lagged, compared with that concerning other important domains of the NHRs. In part, this is because the NTD AFs appear to be unfolded when expressed as recombinant proteins. Recent studies have begun to shed light on the structure and function of the NTD AFs. Recombinant NTD AFs can be made to fold by application of certain osmolytes or when expressed in conjunction with a DNA-binding domain by binding that DNA-binding domain to a DNA response element. The sequence of the DNA binding site may affect the functional state of the AFs domain. If properly folded, NTD AFs can bind certain cofactors and primary transcription factors. Through these, and/or by direct interactions, the NTD AFs may interact with the AF2 domain in the ligand binding, carboxy-terminal portion of the NHRs. We propose models for the folding of the NTD AFs and their protein-protein interactions.

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Comparative analysis of the influence of the high-mobility group box 1 protein on DNA binding and transcriptional activation by the androgen, glucocorticoid, progesterone and mineralocorticoid receptors

Biochemical Journal ◽

10.1042/bj3610097 ◽

2001 ◽

Vol 361 (1) ◽

pp. 97-103 ◽

Cited By ~ 32

Author(s):

Guy VERRIJDT ◽

Annemie HAELENS ◽

Erik SCHOENMAKERS ◽

Wilfried ROMBAUTS ◽

Frank CLAESSENS

Keyword(s):

Androgen Receptor ◽

Comparative Analysis ◽

Dna Binding ◽

Mineralocorticoid Receptor ◽

Hormone Receptors ◽

Steroid Hormone ◽

High Mobility ◽

Steroid Hormone Receptors ◽

High Mobility Group ◽

Mineralocorticoid Receptors

We performed a comparative analysis of the effect of high-mobility group box protein 1 (HMGB1) on DNA binding by the DNA-binding domains (DBDs) of the androgen, glucocorticoid, progesterone and mineralocorticoid receptors. The affinity of the DBDs of the different receptors for the tyrosine aminotransferase glucocorticoid response element, a classical high-affinity binding element, was augmented up to 7-fold by HMGB1. We found no major differences in the effects of HMGB1 on DNA binding between the different steroid hormone receptors. In transient transfection assays, however, HMGB1 significantly enhances the activity of the glucocorticoid and progesterone receptors but not the androgen or mineralocorticoid receptor. We also investigated the effect of HMGB1 on the binding of the androgen receptor DBD to a subclass of directly repeated response elements that is recognized exclusively by the androgen receptor and not by the glucocorticoid, progesterone or mineralocorticoid receptor. Surprisingly, a deletion of 26 amino acid residues from the C-terminal extension of the androgen receptor DBD does not influence DNA binding but destroys its sensitivity to HMGB1. Deletion of the corresponding fragment in the DBDs of the glucocorticoid, progesterone and mineralocorticoid receptor destroyed their DNA binding. This 26-residue fragment is therefore essential for the influence of HMGB1 on DNA recognition by all steroid hormone receptors that were tested. However, it is dispensable for DNA binding by the androgen receptor.

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Nuclear factor I acts as a transcription factor on the MMTV promoter but competes with steroid hormone receptors for DNA binding.

The EMBO Journal ◽

10.1002/j.1460-2075.1990.tb07393.x ◽

1990 ◽

Vol 9 (7) ◽

pp. 2233-2239 ◽

Cited By ~ 91

Author(s):

U. Brüggemeier ◽

L. Rogge ◽

E. L. Winnacker ◽

M. Beato

Keyword(s):

Transcription Factor ◽

Dna Binding ◽

Hormone Receptors ◽

Steroid Hormone ◽

Steroid Hormone Receptors ◽

Nuclear Factor ◽

Factor I ◽

Nuclear Factor I ◽

Mmtv Promoter

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Molecular docking and dynamics simulations in the ligand binding domain of steroid hormone receptors

Pharmacochemistry Library - Trends in Drug Research III ◽

10.1016/s0165-7208(02)80008-3 ◽

2002 ◽

pp. 57-66

Author(s):

Milou Kouwijzer ◽

Jordi Mestres

Keyword(s):

Molecular Docking ◽

Ligand Binding ◽

Hormone Receptors ◽

Steroid Hormone ◽

Binding Domain ◽

Ligand Binding Domain ◽

Steroid Hormone Receptors ◽

Dynamics Simulations ◽

Molecular Docking And Dynamics

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Sequence-Specific Deoxyribonucleic Acid (DNA) Recognition by Steroidogenic Factor 1: A Helix at the Carboxy Terminus of the DNA Binding Domain Is Necessary for Complex Stability

Molecular Endocrinology ◽

10.1210/me.2005-0384 ◽

2006 ◽

Vol 20 (4) ◽

pp. 831-843 ◽

Cited By ~ 38

Author(s):

Tanya H. Little ◽

Yongbo Zhang ◽

Christina K. Matulis ◽

Jennifer Weck ◽

Zhipeng Zhang ◽

...

Keyword(s):

Dna Binding ◽

Dna Sequences ◽

Hormone Receptors ◽

Terminal Segment ◽

Reproductive Hormones ◽

Binding Domain ◽

Proximal Promoter ◽

Dna Binding Domain ◽

Steroidogenic Factor 1 ◽

The Core

Abstract Steroidogenic factor 1 (SF1) is a member of the NR5A subfamily of nuclear hormone receptors and is considered a master regulator of reproduction because it regulates a number of genes encoding reproductive hormones and enzymes involved in steroid hormone biosynthesis. Like other NR5A members, SF1 harbors a highly conserved approximately 30-residue segment called the FTZ-F1 box C-terminal to the core DNA binding domain (DBD) common to all nuclear receptors and binds to 9-bp DNA sequences as a monomer. Here we describe the solution structure of the SF1 DBD in complex with an atypical sequence in the proximal promoter region of the inhibin-α gene that encodes a subunit of a reproductive hormone. SF1 forms a specific complex with the DNA through a bipartite motif binding to the major and minor grooves through the core DBD and the N-terminal segment of the FTZ-F1 box, respectively, in a manner previously described for two other monomeric receptors, nerve growth factor-induced-B and estrogen-related receptor 2. However, unlike these receptors, SF1 harbors a helix in the C-terminal segment of the FTZ-F1 box that interacts with both the core DBD and DNA and serves as an important determinant of stability of the complex. We propose that the FTZ-F1 helix along with the core DBD serves as a platform for interactions with coactivators and other DNA-bound factors in the vicinity.

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Developmental Effects of Ectopic Expression of the Glucocorticoid Receptor DNA Binding Domain Are Alleviated by an Amino Acid Substitution That Interferes with Homeodomain Binding

Molecular and Cellular Biology ◽

10.1128/mcb.19.10.7106 ◽

1999 ◽

Vol 19 (10) ◽

pp. 7106-7122 ◽

Cited By ~ 12

Author(s):

Jun Ming Wang ◽

Gratien G. Préfontaine ◽

Madeleine E. Lemieux ◽

Louise Pope ◽

Marie-Andrée Akimenko ◽

...

Keyword(s):

Transcription Factors ◽

Heat Shock ◽

Dna Binding ◽

Glucocorticoid Receptor ◽

Ectopic Expression ◽

Binding Domain ◽

Steroid Hormone Receptors ◽

Dna Binding Domain ◽

Homeodomain Proteins ◽

Gene Markers

ABSTRACT Steroid hormone receptors are distinguished from other members of the nuclear hormone receptor family through their association with heat shock proteins and immunophilins in the absence of ligands. Heat shock protein association represses steroid receptor DNA binding and protein-protein interactions with other transcription factors and facilitates hormone binding. In this study, we investigated the hormone-dependent interaction between the DNA binding domain (DBD) of the glucocorticoid receptor (GR) and the POU domains of octamer transcription factors 1 and 2 (Oct-1 and Oct-2, respectively). Our results indicate that the GR DBD binds directly, not only to the homeodomains of Oct-1 and Oct-2 but also to the homeodomains of several other homeodomain proteins. As these results suggest that the determinants for binding to the GR DBD are conserved within the homeodomain, we examined whether the ectopic expression of GR DBD peptides affected early embryonic development. The expression of GR DBD peptides in one-cell-stage zebra fish embryos severely affected their development, beginning with a delay in the epibolic movement during the blastula stage and followed by defects in convergence-extension movements during gastrulation, as revealed by the abnormal patterns of expression of several dorsal gene markers. In contrast, embryos injected with mRNA encoding a GR peptide with a point mutation that disrupted homeodomain binding or with mRNA encoding the DBD of the closely related mineralocorticoid receptor, which does not bind octamer factors, developed normally. Moreover, coinjection of mRNA encoding the homeodomain of Oct-2 completely rescued embryos from the effects of the GR DBD. These results highlight the potential of DNA-independent effects of GR in a whole-animal model and suggest that at least some of these effects may result from direct interactions with homeodomain proteins.

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Fos is a preferential target of glucocorticoid receptor inhibition of AP-1 activity in vitro.

Molecular and Cellular Biology ◽

10.1128/mcb.13.6.3782 ◽

1993 ◽

Vol 13 (6) ◽

pp. 3782-3791 ◽

Cited By ~ 103

Author(s):

T K Kerppola ◽

D Luk ◽

T Curran

Keyword(s):

Dna Binding ◽

Glucocorticoid Receptor ◽

Leucine Zipper ◽

Molecular Mechanisms ◽

Hormone Receptors ◽

Transcription Activation ◽

Nuclear Hormone Receptor ◽

Binding Domain ◽

Dna Binding Domain

Several regulatory interactions between the AP-1 and the nuclear hormone receptor families of transcription factors have been reported. However, the molecular mechanisms that underlie these interactions remain unknown, and models derived from transient-transfection experiments are contradictory. We have investigated the effect of the purified glucocorticoid receptor (GR) DNA-binding domain (GR residues 440 to 533 [GR440-533]) on DNA binding and transcription activation by Fos-Jun heterodimers and Jun homodimers. GR440-533 differentially inhibited DNA binding and transcription activation by Fos-Jun heterodimers. Inhibition of Jun homodimers required a 10-fold-higher concentration of GR440-533. An excess of Fos monomers protected Fos-Jun heterodimers from inhibition by GR440-533. Surprisingly, regions outside the leucine zipper and basic region were required for GR inhibition of Fos and Jun DNA binding. The region of GR440-533 required for inhibition of Fos-Jun DNA binding was localized to the zinc finger DNA-binding domain. However, inhibition of Fos-Jun DNA binding was independent of DNA binding by GR440-533. GR440-533 also differentially inhibited Fos-Jun heterodimer binding to the proliferin plfG element. Differential inhibition of DNA binding by different AP-1 family complexes provides a potential mechanism for the diverse interactions between nuclear hormone receptors and AP-1 family proteins at different promoters and in different cell types.

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