scholarly journals Control of Steroid Receptor Dynamics and Function by Genomic Actions of the Cochaperones p23 and Bag-1L

2014 ◽  
Vol 12 (1) ◽  
pp. nrs.12005 ◽  
Author(s):  
Laura Cato ◽  
Antje Neeb ◽  
Myles Brown ◽  
Andrew C. B. Cato
Keyword(s):  
Ligand Binding ◽  
Molecular Chaperones ◽  
Steroid Receptors ◽  
Steroid Receptor ◽  
Combined Effects ◽  
Receptor Dynamics ◽  
Receptor Action ◽  
Dynamics And Function ◽  
And Function ◽  
Receptor Turnover

Molecular chaperones encompass a group of unrelated proteins that facilitate the correct assembly and disassembly of other macromolecular structures of which they themselves do not remain a part. Chaperones associate with a large and diverse set of cofactors termed cochaperones that regulate their function and specificity. Chaperones and cochaperones regulate the activity of several classes of signaling molecules, including steroid receptors. Upon binding ligand, steroid receptors interact with discrete nucleotide sequences within the nucleus to control the expression of diverse physiological and developmental genes. Molecular chaperones and cochaperones are typically known to provide the correct conformation for ligand binding by the steroid receptors. While this contribution is widely accepted, recent studies have reported that they further modulate steroid receptor action outside ligand binding. Specifically, they are thought to contribute to receptor turnover, transport of the receptor to different subcellular localizations, recycling of the receptor on chromatin and stabilization of receptor DNA binding. In addition to these combined effects with molecular chaperones, cochaperones have additional functions that are independent of molecular chaperones, some of which impact steroid receptor action. Two well-studied examples are the cochaperones p23 and Bag-1L, which have been identified as modulators of steroid receptor activity in the nucleus. Understanding details of their regulatory action will provide new therapeutic opportunities for controlling steroid receptor action independent of the widespread effects of molecular chaperones.

Ligand binding to heme proteins: connection between dynamics and function

Biochemistry ◽  
1991 ◽  
Vol 30 (16) ◽  
pp. 3988-4001 ◽  
Author(s):  
Peter J. Steinbach ◽  
Anjum Ansari ◽  
Joel Berendzen ◽  
David Braunstein ◽  
Kelvin Chu ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Heme Proteins ◽  
Dynamics And Function ◽  
And Function

scholarly journals Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs

2003 ◽  
Vol 23 (6) ◽  
pp. 2135-2150 ◽  
Author(s):  
Bin He ◽  
Elizabeth M. Wilson
Keyword(s):  
Ligand Binding ◽  
Steroid Receptors ◽  
Interaction Model ◽  
Hydrophobic Surface ◽  
Steroid Receptor ◽  
Activation Function ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Charged Residues ◽  
Oppositely Charged

ABSTRACT Coactivator recruitment by activation function 2 (AF2) in the steroid receptor ligand binding domain takes place through binding of an LXXLL amphipathic α-helical motif at the AF2 hydrophobic surface. The androgen receptor (AR) and certain AR coregulators are distinguished by an FXXLF motif that interacts selectively with the AR AF2 site. Here we show that LXXLL and FXXLF motif interactions with steroid receptors are modulated by oppositely charged residues flanking the motifs and charge clusters bordering AF2 in the ligand binding domain. An increased number of charged residues flanking AF2 in the ligand binding domain complement the two previously characterized charge clamp residues in coactivator recruitment. The data suggest a model whereby coactivator recruitment to the receptor AF2 surface is initiated by complementary charge interactions that reflect a reversal of the acidic activation domain-coactivator interaction model.

scholarly journals Minireview: The Versatile Roles of Lysine Deacetylases in Steroid Receptor Signaling

2014 ◽  
Vol 28 (5) ◽  
pp. 607-621 ◽  
Author(s):  
Vineela Kadiyala ◽  
Catharine L. Smith
Keyword(s):  
Molecular Chaperones ◽  
Hormone Receptors ◽  
Target Genes ◽  
Steroid Receptors ◽  
Steroid Receptor ◽  
Receptor Signaling ◽  
Receptor Function ◽  
X Receptors ◽  
Lysine Deacetylases

AbstractLysine deacetylases have been known to regulate nuclear receptor function for many years. In the unliganded state, nuclear receptors that form heterodimers with retinoid X receptors, such as the retinoic acid and thyroid hormone receptors, associate with deacetylases to repress target genes. In the case of steroid receptors, binding of an antagonist ligand was initially reported to induce association of deacetylases to prevent activation of target genes. Since then, deacetylases have been shown to have diverse functions in steroid receptor signaling, from regulating interactions with molecular chaperones to facilitating their ability to activate transcription. The purpose of this review is to summarize recent studies on the role of deacetylases in steroid receptor signaling, which show deacetylases to be highly versatile regulators of steroid receptor function.

Osmolytes modify protein dynamics and function of tetrameric lactate dehydrogenase upon pressurization

2019 ◽  
Vol 21 (24) ◽  
pp. 12806-12817 ◽  
Author(s):  
Samy R. Al-Ayoubi ◽  
Paul Hendrik Schummel ◽  
Aline Cisse ◽  
Tilo Seydel ◽  
Judith Peters ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Protein Dynamics ◽  
Combined Effects ◽  
Dynamics And Function ◽  
And Function ◽  
Modify Protein

We present a study of the combined effects of natural cosolvents (TMAO, glycine, urea) and pressure on the activity of the tetrameric enzyme lactate dehydrogenase (LDH).

scholarly journals Steroid Receptor Coactivator 3 Regulates Synaptic Plasticity and Hippocampus-dependent Memory

2021 ◽  
Author(s):  
Hai-Long Zhang ◽  
Bing Zhao ◽  
Pin Yang ◽  
Yin-Quan Du ◽  
Wei Han ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Steroid Hormones ◽  
Hippocampal Neurons ◽  
Short Term Memory ◽  
Steroid Receptors ◽  
Long Term Potentiation ◽  
Steroid Receptor ◽  
Steroid Receptor Coactivator ◽  
Term Potentiation ◽  
And Function

AbstractSteroid hormones play important roles in brain development and function. The signaling of steroid hormones depends on the interaction between steroid receptors and their coactivators. Although the function of steroid receptor coactivators has been extensively studied in other tissues, their functions in the central nervous system are less well investigated. In this study, we addressed the function of steroid receptor coactivator 3 (SRC3) – a member of the p160 SRC protein family that is expressed predominantly in the hippocampus. While hippocampal development was not altered in Src3+/− mice, hippocampus-dependent functions such as short-term memory and spatial memory were impaired. We further demonstrated that the deficient learning and memory in Src3+/− mice was strongly associated with the impairment of long-term potentiation (LTP) at Schaffer Collateral-CA1 synapses. Mechanistic studies indicated that Src3+/− mutation altered the composition of N-methyl-D-aspartate receptor subunits in the postsynaptic densities of hippocampal neurons. Finally, we showed that SRC3 regulated synaptic plasticity and learning mainly dependent on its lysine acetyltransferase activity. Taken together, these results reveal previously unknown functions of SRC3 in the hippocampus and thus may provide insight into how steroid hormones regulate brain function.

scholarly journals Extranuclear Steroid Receptors: Nature and Actions

2007 ◽  
Vol 28 (7) ◽  
pp. 726-741 ◽  
Author(s):  
Stephen R. Hammes ◽  
Ellis R. Levin
Keyword(s):  
Steroid Hormones ◽  
Cell Fate ◽  
Cancer Biology ◽  
Steroid Receptors ◽  
Regulation Of Gene Expression ◽  
Steroid Receptor ◽  
Reproductive Organ ◽  
Structural Determinants ◽  
And Function

Rapid effects of steroid hormones result from the actions of specific receptors localized most often to the plasma membrane. Fast-acting membrane-initiated steroid signaling (MISS) 1leads to the modification of existing proteins and cell behaviors. Rapid steroid-triggered signaling through calcium, amine release, and kinase activation also impacts the regulation of gene expression by steroids, sometimes requiring integration with nuclear steroid receptor function. In this and other ways, the integration of all steroid actions in the cell coordinates outcomes such as cell fate, proliferation, differentiation, and migration. The nature of the receptors is of intense interest, and significant data suggest that extranuclear and nuclear steroid receptor pools are the same proteins. Insights regarding the structural determinants for membrane localization and function, as well as the nature of interactions with G proteins and other signaling molecules in confined areas of the membrane, have led to a fuller understanding of how steroid receptors effect rapid actions. Increasingly, the relevance of rapid signaling for the in vivo functions of steroid hormones has been established. Examples include steroid effects on reproductive organ development and function, cardiovascular responsiveness, and cancer biology. However, although great strides have been made, much remains to be understood concerning the integration of extranuclear and nuclear receptor functions to organ biology. In this review, we highlight the significant progress that has been made in these areas.

scholarly journals DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors

2012 ◽  
Vol 23 (1) ◽  
pp. 188-199 ◽  
Author(s):  
Ali Pedram ◽  
Mahnaz Razandi ◽  
Robert J. Deschenes ◽  
Ellis R Levin
Keyword(s):  
Membrane Trafficking ◽  
Steroid Receptors ◽  
Protein S ◽  
Steroid Receptor ◽  
Sex Steroid ◽  
Target Cells ◽  
Sex Steroid Receptors ◽  
Receptor Localization ◽  
And Function ◽  
Pat Protein

Classical estrogen, progesterone, and androgen receptors (ERs, PRs, and ARs) localize outside the nucleus at the plasma membrane of target cells. From the membrane, the receptors signal to activate kinase cascades that are essential for the modulation of transcription and nongenomic functions in many target cells. ER, PR, and AR trafficking to the membrane requires receptor palmitoylation by palmitoylacyltransferase (PAT) protein(s). However, the identity of the steroid receptor PAT(s) is unknown. We identified the DHHC-7 and -21 proteins as conserved PATs for the sex steroid receptors. From DHHC-7 and -21 knockdown studies, the PATs are required for endogenous ER, PR, and AR palmitoylation, membrane trafficking, and rapid signal transduction in cancer cells. Thus the DHHC-7 and -21 proteins are novel targets to selectively inhibit membrane sex steroid receptor localization and function.

Role of molecular chaperones in steroid receptor action

2004 ◽  
Vol 40 ◽  
pp. 41-58 ◽  
Author(s):  
William B Pratt ◽  
Mario D Galigniana ◽  
Yoshihiro Morishima ◽  
Patrick J M Murphy
Keyword(s):  
Transcriptional Activation ◽  
Protein Trafficking ◽  
Steroid Receptors ◽  
Transcriptional Regulatory ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Receptor Action ◽  
Binding Cleft ◽  
Hsp 90

Unliganded steroid receptors are assembled into heterocomplexes with heat-shock protein (hsp) 90 by a multiprotein chaperone machinery. In addition to binding the receptors at the chaperone site, hsp90 binds cofactors at other sites that are part of the assembly machinery, as well as immunophilins that connect the assembled receptor-hsp90 heterocomplexes to a protein trafficking pathway. The hsp90-/hsp70-based chaperone machinery interacts with the unliganded glucocorticoid receptor to open the steroid-binding cleft to access by a steroid, and the machinery interacts in very dynamic fashion with the liganded, transformed receptor to facilitate its translocation along microtubular highways to the nucleus. In the nucleus, the chaperone machinery interacts with the receptor in transcriptional regulatory complexes after hormone dissociation to release the receptor and terminate transcriptional activation. By forming heterocomplexes with hsp90, the chaperone machinery stabilizes the receptor to degradation by the ubiquitin-proteasome pathway of proteolysis.

Sign in / Sign up

Export Citation Format

Share Document