Affinage

PTGES3

Prostaglandin E synthase 3 · UniProt Q15185

Length
160 aa
Mass
18.7 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PTGES3 (p23) is a co-chaperone of Hsp90 that stabilizes the ATP-bound closed conformation of the Hsp90 dimer, thereby facilitating the maturation, folding, and stabilization of diverse client proteins including steroid hormone receptors (GR, PR, ER, AR), telomerase (hTERT), the aryl hydrocarbon receptor (AHR), and chromatin remodeling complexes such as RSC (PMID:7929183, PMID:16625188, PMID:34937936, PMID:27818141). p23 binds Hsp90 via its N-terminal beta-sandwich domain at the interface of the Hsp90 N-terminal and middle domains in a 2:2 stoichiometry, while its unstructured C-terminal tail mediates Hsp90-independent chaperoning of non-native substrates, direct client contacts (e.g., stabilizing native GR via a C-terminal helix), and protection of clients such as AHR from ubiquitin-mediated degradation (PMID:10543959, PMID:34937936, PMID:29555469, PMID:21183720). p23 additionally promotes receptor–DNA dissociation to dynamically regulate transcription factor occupancy at target genes and modulates telomerase DNA binding and extension in a cell-cycle-dependent manner (PMID:10691735, PMID:17389357). During apoptosis, caspase-3/7 cleavage of p23 at D142/D145 generates a dominant-negative fragment that disrupts Hsp90 function, destabilizes clients including hTERT, and sensitizes cells to death; p23-null mice die perinatally with glucocorticoid receptor-deficient phenotypes, confirming its essential in vivo role in GR signaling rather than prostaglandin E2 biosynthesis (PMID:15483679, PMID:19740745, PMID:17000766, PMID:17438133).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    The identity of p23 as an essential component of the steroid receptor–Hsp90 chaperone machinery was established, resolving whether it was merely an associated protein or a functionally required factor.

    Evidence Immunodepletion of p23 from rabbit reticulocyte lysate abolished progesterone receptor–Hsp90 complex assembly, and add-back of purified p23 rescued activity.

    PMID:7929183

    Open questions at the time
    • Mechanism by which p23 promotes assembly unknown
    • Binding site on Hsp90 not mapped
    • Role with non-steroid receptor clients untested
  2. 1995 High

    p23 entry into the chaperone cycle was placed at a late, ATP-dependent step, establishing that p23 recognizes a specific Hsp90 nucleotide state rather than binding constitutively.

    Evidence Molybdate and AMP-PNP stabilized p23–Hsp90 complexes; geldanamycin displaced p23 from the progesterone receptor complex.

    PMID:8592513

    Open questions at the time
    • Whether p23 binds before or after ATP hydrolysis unresolved
    • Direct binding kinetics not measured
  3. 1996 High

    p23 was shown to possess Hsp90-independent molecular chaperone activity, demonstrating it is not solely an Hsp90 cofactor but a chaperone in its own right.

    Evidence In vitro folding assays showed p23 maintained unfolded substrates in a nonnative, folding-competent state.

    PMID:8939864

    Open questions at the time
    • Substrate specificity undefined
    • Whether in vivo chaperoning is Hsp90-independent not tested
  4. 1999 High

    Domain dissection revealed the structural basis of p23's dual functions: the N-terminal beta-sandwich mediates Hsp90 binding while the disordered C-terminal tail is required for independent chaperoning of non-native substrates.

    Evidence C-terminal truncation mutants retained Hsp90 binding but lost anti-aggregation activity in vitro.

    PMID:10543959

    Open questions at the time
    • Atomic contacts between p23 and substrates unresolved
    • Whether the two functions are separable in vivo not tested
  5. 1999 High

    The client repertoire of p23 was extended beyond steroid receptors to telomerase, establishing that p23/Hsp90 uniquely remains stably associated with the active holoenzyme rather than dissociating after client folding.

    Evidence Co-IP showed p23 and Hsp90 bind hTERT; blocking the interaction inhibited telomerase assembly in vitro; active telomerase from cell extracts co-purified with p23.

    PMID:10197982 PMID:11274138

    Open questions at the time
    • Why p23/Hsp90 remain on telomerase but not on steroid receptors not explained
    • Structural basis of hTERT recognition unknown
  6. 2000 High

    Crystal structure of p23 and functional studies defined the protein fold (antiparallel beta-sandwich) and showed p23 acts on hormone-receptor–DNA ternary complexes to promote receptor dissociation from chromatin, establishing a post-assembly regulatory role.

    Evidence X-ray crystallography of p23; in vitro DNA dissociation assays showed p23 stimulates receptor release from DNA, reversed by coactivator GRIP1.

    PMID:10691735 PMID:10811660

    Open questions at the time
    • How p23-induced DNA dissociation is coupled to the Hsp90 ATPase cycle unclear
    • In vivo genome-wide effects on receptor occupancy not assessed
  7. 2002 High

    The biochemical mechanism of p23's action on Hsp90 was clarified: p23 stabilizes the post-ATP-hydrolysis (ADP-trapped) conformation of Hsp90, producing a long-lived complex that prolongs client engagement.

    Evidence Nucleotide binding and hydrolysis assays with limited proteolysis showed p23 extends the half-life of the nucleotide-bound Hsp90 conformation to ~45 min.

    PMID:12324468

    Open questions at the time
    • Whether stabilization of this state is universally required for all clients untested
    • In vivo kinetics not measured
  8. 2004 High

    Caspase-3/7 cleavage of p23 at D142/D145 during apoptosis was mapped, revealing a mechanism by which apoptotic signaling dismantles the Hsp90 chaperone system.

    Evidence In vitro cleavage of 35S-p23 with recombinant caspases; geldanamycin enhanced cleavage in cells.

    PMID:15483679

    Open questions at the time
    • Functional consequences of cleavage for specific clients not yet tested at this point
    • Whether cleavage is required for apoptosis or is a byproduct unclear
  9. 2006 High

    Three major advances converged: (1) the crystal structure of the full Hsp90–p23/Sba1–ATP complex defined the closed-state architecture; (2) NMR mapped the p23 binding surface to the Hsp90 N/M domain interface with 2:2 stoichiometry; (3) p23-null mice died perinatally with GR-deficient phenotypes, but without evidence of impaired PGE2 synthesis, resolving a long debate about p23's purported prostaglandin synthase activity.

    Evidence X-ray crystallography of yeast Hsp90–Sba1–AMP-PNP; solution NMR titration of human p23–Hsp90; targeted knockout mouse with metabolite analysis.

    PMID:16565516 PMID:16625188 PMID:17000766 PMID:17438133 PMID:21183720

    Open questions at the time
    • Human Hsp90–p23–client ternary structure still lacking
    • How p23 differentially affects different clients structurally unresolved
    • Caspase cleavage of p23 linked to ER stress protection but mechanism of PUMA interaction unclear
  10. 2007 High

    p23/Sba1 was shown to regulate telomerase dynamics at telomeres in vivo: it modulates telomerase DNA dissociation and extension rates in a cell-cycle-dependent manner, extending p23's role from client folding to functional regulation of an assembled enzyme.

    Evidence Genetic manipulation of Sba1 levels in yeast combined with in vitro telomerase assays and ChIP at telomeres.

    PMID:17389357

    Open questions at the time
    • Whether human p23 has identical telomeric dynamics not confirmed
    • Mechanism of cell-cycle-dependent telomere association unknown
  11. 2009 Medium

    The caspase-generated truncation product (Δp23) was shown to act as a dominant-negative inhibitor that decreases hTERT levels and telomerase activity by disrupting Hsp90 phosphorylation, linking apoptotic p23 cleavage to telomere biology.

    Evidence Overexpression of Δp23 reduced Hsp90 Ser-231/263 phosphorylation, hTERT protein, and telomerase activity; sensitized cells to cisplatin.

    PMID:19740745

    Open questions at the time
    • Mechanism by which Δp23 inhibits Hsp90 phosphorylation not defined
    • Whether Δp23 generation is physiologically relevant at endogenous levels unclear
    • Single-lab observation
  12. 2012 Medium

    p23 was found to enhance androgen receptor activity through both Hsp90-dependent (cytoplasmic ligand binding) and Hsp90-independent (nuclear promoter occupancy) mechanisms, establishing that p23 has functional roles beyond its Hsp90 co-chaperone identity.

    Evidence p23 Hsp90-binding mutant still increased AR transcriptional activity; ChIP showed enhanced AR occupancy at target promoters.

    PMID:22899854

    Open questions at the time
    • How p23 enhances AR promoter occupancy mechanistically undefined
    • Whether this applies to other nuclear receptors untested
  13. 2016 High

    p23 was shown to maintain the active pool of the RSC chromatin remodeling complex by triggering its release from nucleosomes while enhancing remodeling, extending the client repertoire to non-receptor chromatin machines; separately, ailanthone binding to p23 was shown to disrupt AR–Hsp90 complexes and trigger ubiquitin-mediated client degradation.

    Evidence In vitro RSC–nucleosome release and remodeling assays with FRAP in vivo; ailanthone direct binding assay with co-IP and proteasome inhibitor rescue.

    PMID:27818141 PMID:27959342

    Open questions at the time
    • Whether p23 regulation of chromatin remodelers is general or RSC-specific unknown
    • Structural basis of p23–RSC interaction unresolved
  14. 2018 High

    p23 was demonstrated to protect AHR from ubiquitin-mediated proteasomal degradation through direct, Hsp90-independent binding via its N-terminal domain, establishing a client-stabilization function independent of the chaperone cycle.

    Evidence Affinity pulldown with purified p23 and AHR fragments mapped the interaction; p23 Hsp90-binding mutants still restored AHR levels; p23 knockdown increased AHR ubiquitination.

    PMID:29555469

    Open questions at the time
    • Whether direct client protection from ubiquitination is a general p23 function unknown
    • E3 ligase(s) involved not identified
  15. 2021 High

    The cryo-EM structure of the human GR–Hsp90–p23 maturation complex provided the first near-atomic view of how p23 directly contacts a folded client: GR-LBD is threaded through the Hsp90 lumen while a p23 C-terminal helix stabilizes native GR, defining the endpoint of the Hsp70-to-Hsp90 client handoff.

    Evidence Cryo-EM structure of GR-LBD–Hsp90–p23 complex with functional ligand-binding validation.

    PMID:34937936

    Open questions at the time
    • Whether the GR threading mechanism applies to all Hsp90 clients unknown
    • Dynamics of client release from the p23-stabilized complex not captured
    • No equivalent structure for non-receptor clients such as hTERT or RSC

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how p23 achieves client specificity among the diverse Hsp90 client repertoire, what structural basis underlies its Hsp90-independent chaperoning and client protection from ubiquitination, and how caspase-generated Δp23 functions as a dominant-negative in physiological apoptotic contexts.
  • No structure of p23 bound to a non-receptor client (e.g., hTERT, RSC)
  • E3 ligases counteracted by p23 not identified
  • In vivo relevance of Δp23 dominant-negative activity at endogenous expression levels unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0044183 protein folding chaperone 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-4839726 Chromatin organization 1
Partners
AHRARBBC3HSP90AA1MLKLNR3C1RIPK3TERT
Complex memberships
Hsp90-p23 co-chaperone complexTelomerase holoenzyme (hTERT-hTR-Hsp90-p23)

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 p23 (PTGES3) is an essential component of the steroid receptor chaperone complex: immunodepletion of p23 from rabbit reticulocyte lysate prevents assembly of progesterone receptor-Hsp90 complexes, and addition of purified p23 restores this activity, demonstrating p23 is required for progesterone receptor maturation. Immunodepletion from cell lysate, in vitro reconstitution, co-immunoprecipitation The Journal of biological chemistry High 7929183
1995 p23 binds to an Hsp90 complex in an ATP-dependent manner; molybdate stabilizes the Hsp90-p23 interaction; geldanamycin disrupts p23-Hsp90 complexes and causes loss of p23, CyP-40, and some Hsp90 from the progesterone receptor complex, placing p23 entry at a late step in receptor assembly. In vitro assembly assay, pharmacological probes (molybdate, AMP-PNP, geldanamycin), co-immunoprecipitation Molecular endocrinology High 8592513
1996 p23 functions as an independent molecular chaperone: in vitro folding assays showed p23 interacts with unfolded substrate proteins to maintain a nonnative folding-competent intermediate, similar to Hsp90/Hsp70 but without ability to completely refold substrates. In vitro chaperone/folding assay Science High 8939864
1998 p23 binds preferentially to the N-terminal ATP-binding domain of Hsp90 (as mapped by co-precipitation with Hsp90 mutants), distinct from TPR-containing accessory proteins which map to the C-terminal half of Hsp90. Co-precipitation with Hsp90 mutants, domain mapping Cell stress & chaperones Medium 9672247
1999 p23 and Hsp90 are required for assembly of active telomerase: both proteins bind to the catalytic subunit hTERT; blockade of this interaction inhibits assembly of active telomerase in vitro; a significant fraction of active telomerase from cell extracts is associated with p23 and Hsp90. Co-immunoprecipitation, in vitro telomerase assembly assay, inhibition studies Genes & development High 10197982
1999 The unstructured C-terminal region of p23 is required for interaction with non-native (client) proteins and prevention of heat-induced aggregation (passive chaperoning), but is dispensable for Hsp90 binding; the structured N-terminal domain is sufficient for Hsp90 interaction. C-terminal truncation mutagenesis, in vitro aggregation assay, co-immunoprecipitation Journal of molecular biology High 10543959
1999 p23 acts as a positive regulator of estrogen receptor (ER) signaling in yeast: yeast p23 (yhp23) colocalizes with ER in vivo and redistributes from cytoplasm to nucleus upon ER coexpression; yhp23 increases ER transcriptional activation by increasing estradiol binding in vivo; overexpression of human p23 in MCF-7 cells increases ER-mediated transcriptional activation. Yeast dosage suppression screen, GFP live imaging, reporter gene assay, overexpression in mammalian cells Molecular and cellular biology Medium 10207098
2000 Crystal structure of human p23 (lacking 35 C-terminal residues) reveals a disulfide-linked dimer in crystal with each subunit forming an antiparallel beta-sandwich; in solution p23 is primarily monomeric. Conserved residues cluster on one face defining a binding surface for Hsp90 or substrates. The C-terminal tail is not needed for Hsp90 binding but is necessary for optimal chaperoning of the progesterone receptor. X-ray crystallography, solution biochemistry, functional assays with truncation mutants The Journal of biological chemistry High 10811660
2000 p23 acts at a late step on hormone-receptor holoreceptor (not aporeceptor) complexes to alter ligand efficacy (transcriptional activation activity); in vitro, p23 preferentially interacts with hormone-receptor-DNA ternary complexes and stimulates receptor dissociation from DNA; this dissociation is reversed by addition of the GRIP1 coactivator fragment, suggesting competition. In vitro binding assay, DNA dissociation assay, mammalian cell transcription assays, yeast assays Genes & development High 10691735
2001 p23 and Hsp90 remain stably associated with active telomerase holoenzyme (unlike other Hsp90 clients from which chaperones dissociate after folding); both specifically bind hTERT and influence its assembly with hTR; Hsp70 associates with hTERT only transiently and dissociates upon active telomerase formation. Co-immunoprecipitation from cell extracts, telomerase activity assays The Journal of biological chemistry High 11274138
2002 p23 binding to Hsp90 stabilizes the ATP-induced conformational state of Hsp90; both p23 and molybdate enhance and stabilize the nucleotide-bound (ADP-trapped) state of Hsp90, and their effects are additive; the p23-Hsp90 complex formed after ATP hydrolysis is stable with a half-life of ~45 min at 30°C. In vitro binding assay, nucleotide binding/hydrolysis assays, limited proteolysis The Journal of biological chemistry High 12324468
2003 Mutations in p23 that reduce or increase ER signal transduction correlate with their association with Hsp90; a C-terminal tail mutation confers dominant inhibitory effect on ER transcriptional activation and binds Hsp90 in its non-ATP-bound state (unlike wild-type p23 which requires ATP-bound Hsp90); a distinct surface on one face of p23 mediates ER signaling. Random mutagenesis screen in yeast, in vitro co-immunoprecipitation, molecular modeling with crystal structure The Journal of biological chemistry High 12835317
2003 p23 enhances formation of the aryl hydrocarbon receptor (AhR)-DNA complex: fractionation and immunodepletion studies showed the centricon-10 retentate fraction (containing p23 but not Hsp90) restores gel shift complex formation; purified bacterially expressed p23 restores AhR/Arnt DRE-binding activity and acts at the heterodimerization step in an Hsp90-dependent manner. Fractionation, immunodepletion, EMSA, purified protein reconstitution Biochemical pharmacology Medium 12623125
2004 p23 is cleaved at D142 and D145 by caspase-7 and caspase-3 during apoptosis (mapped by in vitro cleavage of 35S-p23 with recombinant caspases); the Hsp90 inhibitor geldanamycin enhances caspase-dependent p23 cleavage both by rendering p23 more susceptible to caspases and by enhancing caspase activation. In vitro caspase cleavage assay with 35S-labeled p23, pharmacological inhibition, cell-based apoptosis assays Leukemia High 15483679
2006 p23 is required for perinatal survival in mice: p23 null embryos display underdeveloped airspaces and reduced surfactant gene expression; p23-null fibroblasts have a defective glucocorticoid receptor response, consistent with p23's role in assembly of GR-Hsp90 complexes. Gene trap knockout mouse, histology, gene expression analysis, cell-based GR assay Molecular and cellular biology High 17000766
2006 p23 is cleaved during ER stress-induced cell death by caspase-3 and/or caspase-7 near the C-terminus; blocking the caspase cleavage site decreases ER stress-induced cell death; p23 co-immunoprecipitates with the BH3-only protein PUMA in untreated cells, and prolonged ER stress disrupts this interaction; siRNA knockdown of p23 enhances ER stress-induced cell death, demonstrating an HSP90-independent protective role for p23. Caspase inhibitor studies, site-directed mutagenesis (caspase site), co-immunoprecipitation, siRNA knockdown, cell death assays Cell death and differentiation High 16195741
2006 The N-terminal nucleotide-binding domain of Hsp90 triggers binding to p23: NMR titration showed the Hsp90 N-domain (with ATP) and middle domain together form the p23 binding interface; Hsp90 and p23 form a 2:2 complex via positively cooperative mechanism (shown by native mass spectrometry); p23-induced NMR shifts map to Hsp90's ATP-binding lid and middle domain, indicating p23 causes allosteric conformational changes in Hsp90. Solution NMR (isoleucine labeling), native mass spectrometry, domain dissection Proceedings of the National Academy of Sciences of the United States of America High 21183720
2006 NMR solution mapping of p23-Hsp90 interaction: the middle (M) domain of Hsp90 is the primary binding site for p23 (not the N-terminal domain alone); the p23 binding surface includes C-terminal sequence of p23 and a contiguous N-terminal beta-hairpin; Aha1 (which binds the M domain) displaces p23 from Hsp90. Solution NMR (15N-1H HSQC titration), domain dissection of Hsp90 The Journal of biological chemistry High 16565516
2006 Crystal structure of full-length yeast Hsp90 in complex with ATP analogue and the co-chaperone p23/Sba1 (ortholog of human PTGES3/p23) reveals the 'closed' state architecture: p23/Sba1 stabilizes the closed ATP-bound Hsp90 dimer; the complex does not enclose client proteins but provides a bipartite binding surface coupled to the ATPase cycle. X-ray crystallography of full-length Hsp90-ATP-p23 complex Nature High 16625188
2007 The p23 molecular chaperone promotes telomerase DNA dissociation and functional telomere maintenance: yeast p23 ortholog Sba1p modulates telomerase DNA binding and extension activities in vitro; Sba1p shows cell cycle-dependent telomere association paralleling telomerase; changes in Sba1 levels alter telomere occupancy by telomerase and extension rate of shortened telomere in vivo. Genetic manipulation of Sba1 levels in yeast, in vitro telomerase binding/extension assay, ChIP Proceedings of the National Academy of Sciences of the United States of America High 17389357
2007 cPGES/p23 (PTGES3) knockout mice show perinatal lethality with features similar to glucocorticoid receptor-deficient neonates (retarded lung development, failure to induce gluconeogenic enzymes), but analysis of arachidonic acid metabolites failed to support a role for p23 in PGE2 biosynthesis in vivo, indicating GR stabilization is a primary in vivo function. Targeted knockout mouse, biochemical analysis of arachidonic acid metabolites, gene expression analysis Molecular and cellular biology High 17438133
2009 A truncated form of p23 (Delta p23, generated by caspase cleavage) down-regulates telomerase activity via disruption of Hsp90 function: overexpression of Delta p23 decreases hTERT protein levels and telomerase activity; Delta p23 reduces phosphorylation of Hsp90 at Ser-231 and Ser-263, residues important for telomerase activation; truncated p23 inhibits cell growth and sensitizes to cisplatin. Overexpression of truncation mutants, site-directed mutagenesis of Hsp90 phosphorylation sites, telomerase activity assay, cell proliferation assay The Journal of biological chemistry Medium 19740745
2013 Gedunin directly binds to p23 and inactivates it: molecular docking and mutational analysis mapped the gedunin-binding site on p23; gedunin inhibits p23 chaperoning activity, blocks p23 interaction with Hsp90 in cells, and interferes with p23-mediated gene regulation; p23 inactivation leads to caspase-7-mediated cleavage of p23 at its C-terminus and cancer cell apoptosis. Molecular docking, site-directed mutagenesis, in vitro chaperoning assay, co-immunoprecipitation, cell death assays The Journal of biological chemistry High 23355466
2014 PHD2 (the oxygen sensor EGLN1) interacts with p23 via a PXLE motif on PHD2 binding to p23's zinc finger region; the Tibetan PHD2 haplotype (D4E/C127S) strikingly diminishes PHD2-p23 interaction, resulting in impaired PHD2 down-regulation of the HIF pathway; this defective p23 binding depends on both substitutions. Co-immunoprecipitation, site-directed mutagenesis, HIF pathway reporter assay The Journal of biological chemistry Medium 24711448
2016 Ailanthone (AIL) binds to p23 (PTGES3) and prevents AR's interaction with HSP90, causing disruption of the AR-chaperone complex followed by ubiquitin/proteasome-mediated degradation of AR and other p23 clients (AKT, Cdk4); this demonstrates p23 is required for maintaining these client proteins in a stable, active state. Direct binding assay, co-immunoprecipitation, proteasome inhibitor rescue, cell-based degradation assay Nature communications High 27959342
2016 Hsp90 and p23 maintain the active pool of the RSC chromatin remodeling complex: both trigger release of RSC from DNA/nucleosomes; p23 additionally enhances nucleosome remodeling prior to complex discharge; in vivo, RSC mobility and remodeling function are chaperone-dependent. In vitro RSC-DNA/nucleosome release assay, in vivo RSC mobility (FRAP), chromatin remodeling assay, genetic manipulation of chaperones Molecular cell High 27818141
2018 p23 protects the aryl hydrocarbon receptor (AHR) from ubiquitin-mediated proteasomal degradation via a direct Hsp90-independent interaction: p23 directly binds AHR (interaction surface mapped to AHR aa 1–216 and p23 aa 1–110 by GST/thioredoxin pulldown); p23 mutants with impaired Hsp90 binding still restore AHR levels; p23 knockdown promotes AHR ubiquitination. siRNA knockdown, co-immunoprecipitation, affinity pulldown with purified fusion proteins, ubiquitination assay, p23 mutant expression Biochemical pharmacology High 29555469
2020 HSP90/p23 complex acts as a novel RIPK3- and MLKL-interacting complex during necroptosis of endothelial cells: co-immunoprecipitation demonstrated p23 and Hsp90 interact with both RIPK3 and MLKL; this complex plays an important role in RIP-MLKL-mediated necroptosis, inflammation, and endothelial dysfunction in pulmonary vasculature. Co-immunoprecipitation, mouse LPS-ARDS model, pharmacological inhibition, cell-based necroptosis assays Journal of molecular medicine Medium 32072232
2021 Cryo-EM structure of human GR-Hsp90-p23 maturation complex reveals: GR ligand-binding domain is restored to folded, ligand-bound conformation while threaded through the Hsp90 lumen; p23 directly stabilizes native GR via a C-terminal helix, resulting in enhanced ligand binding; this defines the mechanism of chaperone-mediated GR remodeling from Hsp70-loaded (inactive) to Hsp90-p23 (active) state. Cryo-electron microscopy, structural analysis, functional ligand binding assay Nature High 34937936
2012 p23 increases androgen receptor (AR) activity via steps both in the cytoplasm (increasing ligand-binding capacity) and nucleus (enhancing AR occupancy at target promoters); AR and p23 can interact independently of Hsp90; a p23 mutant unable to bind Hsp90 still increases AR activity, demonstrating Hsp90-independent p23-AR function. Co-immunoprecipitation, reporter gene assay, chromatin immunoprecipitation (ChIP), p23 Hsp90-binding mutant expression Molecular endocrinology Medium 22899854

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 758 16625188
1999 Functional requirement of p23 and Hsp90 in telomerase complexes. Genes & development 444 10197982
2007 TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature 390 17237767
1996 Molecular chaperone machines: chaperone activities of the cyclophilin Cyp-40 and the steroid aporeceptor-associated protein p23. Science (New York, N.Y.) 302 8939864
1999 A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. Blood 245 10216106
1995 Binding of p23 and hsp90 during assembly with the progesterone receptor. Molecular endocrinology (Baltimore, Md.) 228 8592513
1993 Bcl-2 associates with the ras-related protein R-ras p23. Nature 228 8232588
1994 A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23. The Journal of biological chemistry 199 7929183
2001 Stable association of hsp90 and p23, but Not hsp70, with active human telomerase. The Journal of biological chemistry 188 11274138
2002 Heterozygous submicroscopic inversions involving olfactory receptor-gene clusters mediate the recurrent t(4;8)(p16;p23) translocation. American journal of human genetics 157 12058347
1998 Differential interactions of p23 and the TPR-containing proteins Hop, Cyp40, FKBP52 and FKBP51 with Hsp90 mutants. Cell stress & chaperones 151 9672247
1994 Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohistochemistry. Blood 144 7949120
1993 Molecular cloning, characterization, subcellular localization and dynamics of p23, the mammalian KDEL receptor. The Journal of cell biology 143 8380600
2000 The p23 molecular chaperones act at a late step in intracellular receptor action to differentially affect ligand efficacies. Genes & development 130 10691735
1997 Involvement of the transmembrane protein p23 in biosynthetic protein transport. The Journal of cell biology 126 9382861
2002 p23 and HSP20/alpha-crystallin proteins define a conserved sequence domain present in other eukaryotic protein families. FEBS letters 122 12372593
2021 Structure of Hsp90-p23-GR reveals the Hsp90 client-remodelling mechanism. Nature 114 34937936
2000 Crystal structure and activity of human p23, a heat shock protein 90 co-chaperone. The Journal of biological chemistry 113 10811660
1989 The growth-related protein P23 of the Ehrlich ascites tumor: translational control, cloning and primary structure. Biochemistry international 104 2479380
2013 Gedunin inactivates the co-chaperone p23 protein causing cancer cell death by apoptosis. The Journal of biological chemistry 101 23355466
2010 N-terminal domain of human Hsp90 triggers binding to the cochaperone p23. Proceedings of the National Academy of Sciences of the United States of America 99 21183720
1992 The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. Blood 99 1586743
2000 The p24 family member p23 is required for early embryonic development. Current biology : CB 97 10660306
1999 Role for Hsp90-associated cochaperone p23 in estrogen receptor signal transduction. Molecular and cellular biology 97 10207098
1997 Mapping of the gene encoding human beta-defensin-2 (DEFB2) to chromosome region 8p22-p23.1. Genomics 97 9441752
2003 p23, a simple protein with complex activities. Cell stress & chaperones 94 14627195
1998 Genetic and biochemical analysis of p23 and ansamycin antibiotics in the function of Hsp90-dependent signaling proteins. Molecular and cellular biology 93 9584173
2002 The influence of ATP and p23 on the conformation of hsp90. The Journal of biological chemistry 89 12324468
2013 Dysregulation of glucocorticoid receptor co-factors FKBP5, BAG1 and PTGES3 in prefrontal cortex in psychotic illness. Scientific reports 87 24345775
2001 Recruitment to Golgi membranes of ADP-ribosylation factor 1 is mediated by the cytoplasmic domain of p23. The EMBO journal 84 11726511
1999 Intracellular localization and in vivo trafficking of p24A and p23. Journal of cell science 84 9914165
2016 Ailanthone targets p23 to overcome MDV3100 resistance in castration-resistant prostate cancer. Nature communications 83 27959342
1999 An unstructured C-terminal region of the Hsp90 co-chaperone p23 is important for its chaperone function. Journal of molecular biology 82 10543959
1993 Molecular characterization and expression of p23 (OspC) from a North American strain of Borrelia burgdorferi. Infection and immunity 76 8225587
2008 Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1-p23.1, 4q21.21-q22.1, 6q26-q27, and 21q2. American journal of medical genetics. Part A 73 18536050
1999 GTP-dependent binding of ADP-ribosylation factor to coatomer in close proximity to the binding site for dilysine retrieval motifs and p23. The Journal of biological chemistry 73 10318838
2003 A case of a diffuse large B-cell lymphoma of plasmablastic type associated with the t(2;5)(p23;q35) chromosome translocation. The American journal of surgical pathology 71 14576483
2007 Dual roles of the transmembrane protein p23/TMP21 in the modulation of amyloid precursor protein metabolism. Molecular neurodegeneration 68 17288597
2006 The Hsp90 cochaperone p23 is essential for perinatal survival. Molecular and cellular biology 68 17000766
2007 cPGES/p23 is required for glucocorticoid receptor function and embryonic growth but not prostaglandin E2 synthesis. Molecular and cellular biology 66 17438133
2002 The p23 protein of citrus tristeza virus controls asymmetrical RNA accumulation. Journal of virology 64 11752137
1986 Human ornithine decarboxylase sequences map to chromosome regions 2pter----p23 and 7cen----qter but are not coamplified with the NMYC oncogene. Cytogenetics and cell genetics 63 3755388
2014 Defective Tibetan PHD2 binding to p23 links high altitude adaption to altered oxygen sensing. The Journal of biological chemistry 62 24711448
1997 p23, a major COPI-vesicle membrane protein, constitutively cycles through the early secretory pathway. Proceedings of the National Academy of Sciences of the United States of America 62 9326620
1996 The involvement of p23, hsp90, and immunophilins in the assembly of progesterone receptor complexes. The Journal of steroid biochemistry and molecular biology 62 8603045
2006 Coupling endoplasmic reticulum stress to the cell-death program: a novel HSP90-independent role for the small chaperone protein p23. Cell death and differentiation 60 16195741
2000 The transmembrane protein p23 contributes to the organization of the Golgi apparatus. Journal of cell science 60 10683152
2004 Acute myeloid leukemia with t(6;9)(p23;q34) is associated with dysplasia and a high frequency of flt3 gene mutations. American journal of clinical pathology 58 15362364
1996 Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease. Blood 58 8562933
1996 Detection of t(2;5)(p23;q35) translocation by reverse transcriptase polymerase chain reaction and in situ hybridization in CD30-positive primary cutaneous lymphoma and lymphomatoid papulosis. The American journal of pathology 57 8701987
1998 Bell peppers (Capsicum annuum) express allergens (profilin, pathogenesis-related protein P23 and Bet v 1) depending on the horticultural strain. International archives of allergy and immunology 56 9652302
2006 Localization of sites of interaction between p23 and Hsp90 in solution. The Journal of biological chemistry 53 16565516
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