Cited by 126Heat shock proteins researchEstrogen and related hormone effectsGenomics and Chromatin Dynamics

The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index, and 1 are not checked yet.

Role for Hsp90-Associated Cochaperone p23 in Estrogen Receptor Signal Transduction

Open access

Knoblauch, Roland, Garabedian, Michael J.·1999·Molecular and Cellular Biology

DOI 10.1128/mcb.19.5.3748PMC PMC84199

Open this paper in CoChat — free account

Abstract

The mechanism of signal transduction by the estrogen receptor (ER) is complex and not fully understood. In addition to the ER, a number of accessory proteins are apparently required to efficiently transduce the steroid hormone signal. In the absence of estradiol, the ER, like other steroid receptors, is complexed with Hsp90 and other molecular chaperone components, including an immunophilin, and p23. This Hsp90-based chaperone complex is thought to repress the ER's transcriptional regulatory activities while maintaining the receptor in a conformation that is competent for high-affinity steroid binding. However, a role for p23 in ER signal transduction has not been demonstrated. Using a mutant ER (G400V) with decreased hormone binding capacity as a substrate in a dosage suppression screen in yeast cells (Saccharomyces cerevisiae), we identified the yeast homologue of the human p23 protein (yhp23) as a positive regulator of ER function. Overexpression of yhp23 in yeast cells increases ER transcriptional activation by increasing estradiol binding in vivo. Importantly, the magnitude of the effect of yhp23 on ER transcriptional activation is inversely proportional to the concentration of both ER and estradiol in the cell. Under conditions of high ER expression, ER transcriptional activity is largely independent of yhp23, whereas at low levels of ER expression, ER transcriptional activation is primarily dependent on yhp23. The same relationship holds for estradiol levels. We further demonstrate that yhp23 colocalizes with the ER in vivo. Using a yhp23-green fluorescent protein fusion protein, we observed a redistribution of yhp23 from the cytoplasm to the nucleus upon coexpression with ER. This nuclear localization of yhp23 was reversed by the addition of estradiol, a finding consistent with yhp23's proposed role as part of the aporeceptor complex. Expression of human p23 in yeast partially complements the loss of yhp23 function with respect to ER signaling. Finally, ectopic expression of human p23 in MCF-7 breast cancer cells increases both hormone-dependent and hormone-independent transcriptional activation by the ER. Together, these results strongly suggest that p23 plays an important role in ER signal transduction.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1128/mcb.19.5.3748

Cites

59 of 60 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Molecular basis of agonism and antagonism in the oestrogen receptor
Brzozowski, A. M., Pike, A. C. W., Dauter, Z., Hubbard, R. E., Bonn, T., Engström, O., Öhman, L., Greene, G. L., Gustafsson, J.-Å., & Carlquist, M. (1997) · Nature · doi:10.1038/39645 · Cited by 3,355
Sequence and Characterization of a Coactivator for the Steroid Hormone Receptor Superfamily
Oñate, S. A., Tsai, S. Y., Tsai, M., & O’Malley, B. W. (1995) · Science · doi:10.1126/science.270.5240.1354 · Cited by 2,398
Steroid Receptor Interactions with Heat Shock Protein and Immunophilin Chaperones*
Pratt, W. B., & Toft, D. O. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.3.0303 · Cited by 1,791
Monoclonal antibodies localize oestrogen receptor in the nuclei of target cells
King, W. J., & Greene, G. L. (1984) · Nature · doi:10.1038/307745a0 · Cited by 1,408
Functional domains of the human estrogen receptor
Kumar, V., Green, S., Stack, G., Berry, M., Jin, J.-R., & Chambon, P. (1987) · Cell · doi:10.1016/0092-8674(87)90581-2 · Cited by 1,316
The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer
Kumar, V., & Chambon, P. (1988) · Cell · doi:10.1016/0092-8674(88)90017-7 · Cited by 1,240
Activation of the unliganded estrogen receptor by EGF involves the MAP kinase pathway and direct phosphorylation.
Bunone, G., Briand, P.-A., Miksicek, R. J., & Picard, D. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00571.x · Cited by 985
Nuclear localization of unoccupied oestrogen receptors
Welshons, W. V., Lieberman, M. E., & Gorski, J. (1984) · Nature · doi:10.1038/307747a0 · Cited by 870
Reduced levels of hsp90 compromise steroid receptor action in vivo
Picard, D., Khursheed, B., Garabedian, M. J., Fortin, M. G., Lindquist, S., & Yamamoto, K. R. (1990) · Nature · doi:10.1038/348166a0 · Cited by 787 · cited 3×
“reduced in yeast strains expressing only 5% of the wt level of Hsp82 (44).”
BackgroundInfluentialSelf-citation
GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors.
Hong, H., Kohli, K. K., Trivedi, A. A., Johnson, D. L., & Stallcup, M. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4948 · Cited by 694
Molecular Mechanisms of Estrogen Carcinogenesis
Yager, J. D., & Leihr, J. G. (1996) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.36.040196.001223 · Cited by 671
The hormone-binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function
Webster, N. J. G. (1988) · Cell · doi:10.1016/0092-8674(88)90552-1 · Cited by 580
GRIP1, a Transcriptional Coactivator for the AF-2 Transactivation Domain of Steroid, Thyroid, Retinoid, and Vitamin D Receptors
Hong, H., Kohli, K. K., Garabedian, M. J., & Stallcup, M. R. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.5.2735 · Cited by 553
Self-citation
The common 90‐kd protein component of non‐transformed ‘8S’ steroid receptors is a heat‐shock protein.
CATELLI, M. G., Binart, N., Jung‐Testas, I., Renoir, J., Baulieu, E. E., Feramisco, J. R., & Wj, W. (1985) · The EMBO Journal · doi:10.1002/j.1460-2075.1985.tb04055.x · Cited by 516
The hsp90-based Chaperone System: Involvement in Signal Transduction from a Variety of Hormone and Growth Factor Receptors
Pratt, W. B. (1998) · Experimental Biology and Medicine · doi:10.3181/00379727-217-44252 · Cited by 446
The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties.
Tora, L., Mullick, A., METZGER, D., Ponglikitmongkol, M., Park, I., & Chambon, P. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03604.x · Cited by 414
The human oestrogen receptor functions in yeast
METZGER, D., White, J. H., & Chambon, P. (1988) · Nature · doi:10.1038/334031a0 · Cited by 392
Estrogen receptor gene disruption: molecular characterization and experimental and clinical phenotypes.
Korach, K. S., Couse, J. F., Curtis, S. W., Washburn, T. F., Lindzey, J. K., Kimbro, K. S., Eddy, E. M., Migliaccio, S., Snedeker, S. M., Lubahn, D. B., et al. (1996) · PubMed · Cited by 370
Molecular Chaperone Machines: Chaperone Activities of the Cyclophilin Cyp-40 and the Steroid Aporeceptor-Associated Protein p23
Freeman, B. C., Toft, D. O., & Morimoto, R. I. (1996) · Science · doi:10.1126/science.274.5293.1718 · Cited by 370 · cited 2×
“Since p23 has been proposed to have chaperone-like activities (17), we hypothesized that it may play a role in the proper folding of the AF-2 domain around estradiol during the process of steroid binding.”
Background
Members of the steroid hormone receptor superfamily interact with TFIIB (S300-II).
Ing, N. H., Beekman, J. M., Tsai, S. Y., Tsai, M., & O’Malley, B. W. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37087-5 · Cited by 336
Antagonism of glucocorticoid receptor transcriptional activation by the c-Jun N-terminal kinase
Rogatsky, I., Logan, S. K., & Garabedian, M. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2050 · Cited by 297
Self-citation
Estrogens, the immune response and autoimmunity.
Cutolo, M., Sulli, A., SERIOLO, B., Accardo, S., & Masi, A. T. (1995) · PubMed · Cited by 288
Folding of the Glucocorticoid Receptor by the Heat Shock Protein (hsp) 90-based Chaperone Machinery
Dittmar, K. D., Demady, D. R., Stancato, L. F., Krishna, P., & Pratt, W. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.34.21213 · Cited by 265
Nucleotides and Two Functional States of hsp90
Sullivan, W., Stensgard, B. A., Caucutt, G., Bartha, B. B., McMahon, N., Alnemri, E. S., Litwack, G., & Toft, D. O. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.12.8007 · Cited by 235
Binding of p23 and hsp90 during assembly with the progesterone receptor.
Johnson, J. L., & Toft, D. O. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.6.8592513 · Cited by 233
A novel chaperone complex for steroid receptors involving heat shock proteins, immunophilins, and p23.
Johnson, J. L., & Toft, D. O. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31487-4 · Cited by 229
Characterization of the Amino-terminal Transcriptional Activation Function of the Human Estrogen Receptor in Animal and Yeast Cells
METZGER, D., Ali, S., Bornert, J., & Chambon, P. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.16.9535 · Cited by 228
Role of the Protein Chaperone YDJ1 in Establishing Hsp90-Mediated Signal Transduction Pathways
Kimura, Y., Yahara, I., & Lindquist, S. L. (1995) · Science · doi:10.1126/science.7761857 · Cited by 228
A Cyclophilin Function in Hsp90-Dependent Signal Transduction
Duina, A. A., Foreman, H.-C. C., Marsh, J. A., Lindquist, S. L., & Gaber, R. F. (1996) · Science · doi:10.1126/science.274.5293.1713 · Cited by 224
In Vivo Analysis of the Hsp90 Cochaperone Sti1 (p60)
Foreman, H.-C. C., Nathan, D. F., & Lindquist, S. L. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.1.318 · Cited by 214
Characterization of a novel 23-kilodalton protein of unactive progesterone receptor complexes
Johnson, J. L., Beito, T., Krco, C., & Toft, D. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1956-1963.1994 · Cited by 204
Estradiol-induced Phosphorylation of Serine 118 in the Estrogen Receptor Is Independent of p42/p44 Mitogen-activated Protein Kinase
Joel, P. B., Traish, A. M., & Lannigan, D. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.13317 · Cited by 201
Characterization of a Novel 23-Kilodalton Protein of Unactive Progesterone Receptor Complexes
Johnson, J. L., Beito, T. G., Krco, C. J., & Toft, D. O. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.3.1956 · Cited by 197
Yeast Two-Hybrid System
(2024) · Springer eBooks · doi:10.1007/978-981-99-9283-6_2979 · Cited by 191
The cyclophilin component of the unactivated estrogen receptor contains a tetratricopeptide repeat domain and shares identity with p59 (FKBP59)
Ratajczak, T., Carrello, A., Mark, P. J., Warner, B., Simpson, R. J., Moritz, R. L., & House, A. K. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)38636-3 · Cited by 187
Folding of the Glucocorticoid Receptor by the Reconstituted hsp90-based Chaperone Machinery
Dittmar, K. D., & Pratt, W. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.20.13047 · Cited by 183
Cyclophilin 40 (CyP-40), Mapping of Its hsp90 Binding Domain and Evidence That FKBP52 Competes with CyP-40 for hsp90 Binding
Ratajczak, T., & Carrello, A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.6.2961 · Cited by 175
The Role of DnaJ-like Proteins in Glucocorticoid Receptor·hsp90 Heterocomplex Assembly by the Reconstituted hsp90·p60·hsp70 Foldosome Complex
Dittmar, K. D., Banach, M., Galigniana, M. D., & Pratt, W. B. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.13.7358 · Cited by 162
The Function of Steroid Hormone Receptors Is Inhibited by the hsp90-specific Compound Geldanamycin
Segnitz, B., & Gehring, U. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.30.18694 · Cited by 160
LEM1, an ATP-binding-cassette transporter, selectively modulates the biological potency of steroid hormones.
Kralli, A., Bohen, S. P., & Yamamoto, K. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4701 · Cited by 160
Conservation of Hsp90 macromolecular complexes in Saccharomyces cerevisiae.
Chang, H.-C., & Lindquist, S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31486-2 · Cited by 158
Reconstitution of the Steroid Receptor·hsp90 Heterocomplex Assembly System of Rabbit Reticulocyte Lysate
Dittmar, K. D., Hutchison, K. A., Owens-Grillo, J. K., & Pratt, W. B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.22.12833 · Cited by 157
SBA1 Encodes a Yeast Hsp90 Cochaperone That Is Homologous to Vertebrate p23 Proteins
Fang, Y., Fliss, A., Rao, J., & Caplan, A. J. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.3727 · Cited by 152
The 23-kDa Acidic Protein in Reticulocyte Lysate Is the Weakly Bound Component of the hsp Foldosome That Is Required for Assembly of the Glucocorticoid Receptor into a Functional Heterocomplex with hsp90
Hutchison, K. A., Stancato, L. F., Owens-Grillo, J. K., Johnson, J. L., Krishna, P., Toft, D. O., & Pratt, W. B. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18841 · Cited by 125
Estrogen Stakes Claim to Cognition
Wickelgren, I. (1997) · Science · doi:10.1126/science.276.5313.675 · Cited by 119
Genetic and Biochemical Analysis of p23 and Ansamycin Antibiotics in the Function of Hsp90-Dependent Signaling Proteins
Bohen, S. P. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.6.3330 · Cited by 106
Promoter specificity of the two transcriptional activation functions of the human oestrogen receptor in yeast
METZGER, D., Losson, R., Bornert, J., Lemoine, Y., & Chambon, P. (1992) · Nucleic Acids Research · doi:10.1093/nar/20.11.2813 · Cited by 104
Genetic dissection of the signaling domain of a mammalian steroid receptor in yeast.
Garabedian, M. J., & Yamamoto, K. R. (1992) · Molecular Biology of the Cell · doi:10.1091/mbc.3.11.1245 · Cited by 103
Self-citation
All of the factors required for assembly of the glucocorticoid receptor into a functional heterocomplex with heat shock protein 90 are preassociated in a self-sufficient protein folding structure, a “foldosome”.
Hutchison, K. A., Dittmar, K. D., & Pratt, W. B. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)46871-8 · Cited by 101
The Yeast Two-Hybrid System
Kohalmi, S. E., Nowak, J., & Crosby, W. L. (1997) · CRC Press eBooks · doi:10.1201/b16830-8 · Cited by 89
Mechanism of Estrogen Receptor-Dependent Transcription in a Cell-Free System
Elliston, J. F., Fawell, S. E., Klein‐Hitpaß, L., Tsai, S. Y., Tsai, M., Parker, M. G., & O’Malley, B. W. (1990) · Molecular and Cellular Biology · doi:10.1128/mcb.10.12.6607 · Cited by 86
Mutational analysis of Hsp90α dimerization and subcellular localization: dimer disruption does not impede ‘in vivo’ interaction with estrogen receptor
Meng, X., Devin, J., Sullivan, W. P., Toft, D. O., Baulieu, É.-É., & CATELLI, M. G. (1996) · Journal of Cell Science · doi:10.1242/jcs.109.7.1677 · Cited by 65
Subunit structure of the nonactivated human estrogen receptor.
Segnitz, B., & Gehring, U. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.6.2179 · Cited by 64
Sequence of a 10·7 kb segment of yeast chromosome XI identifies the APN1 and the BAF1 loci and reveals one tRNA gene and several new open reading frames including homologs to RAD2 and kinases
Jacquier, A., Legrain, P., & Dujon, B. (1992) · Yeast · doi:10.1002/yea.320080207 · Cited by 48
Selective Interaction of hsp90 with an Estrogen Receptor Ligand-binding Domain Containing a Point Mutation
Aumais, J. P., Lee, H. S., Lin, R., & White, J. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.18.12229 · Cited by 37
Hormone-dependent Transactivation by Estrogen Receptor Chimeras That Do Not Interact with hsp90
Lee, H. S., Aumais, J. P., & White, J. H. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.42.25727 · Cited by 27
Yeast molecular chaperones and the mechanism of steroid hormone action
CAPLAN, A. (1997) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(97)00079-9 · Cited by 19
Estrogen and bone: New pieces to the puzzle
Raisz, L. G. (1996) · Nature Medicine · doi:10.1038/nm1096-1077 · Cited by 11
Why cardiologists should be interested in estrogen
Ginsburg, G. S., & Douglas, P. S. (1996) · The American Journal of Cardiology · doi:10.1016/s0002-9149(96)00365-7 · Cited by 3
Untitled work
(1996) · doi:10.1379/1466-1268(1996)001

Research works printed but not linked: 1

10.1128/mcb.10.12.6607-6612.1990 · DOI

Sorted by citations

Endocrine Disrupting Chemicals Targeting Estrogen Receptor Signaling: Identification and Mechanisms of Action
Shanle, E. K., & Xu, W. (2010) · Chemical Research in Toxicology · doi:10.1021/tx100231n · Cited by 521
CAR and PXR: The xenobiotic-sensing receptors☆
Timsit, Y., & Negishi, M. (2006) · Steroids · doi:10.1016/j.steroids.2006.12.006 · Cited by 423
A Tissue-Specific Coactivator of Steroid Receptors, Identified in a Functional Genetic Screen
Knutti, D., Kaul, A., & Kralli, A. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.7.2411-2422.2000 · Cited by 286
Nuclear receptors CAR and PXR: Molecular, functional, and biomedical aspects
di Masi, A., Marinis, E. D., Ascenzi, P., & Marino, M. (2009) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2009.04.002 · Cited by 288
Role of hsp90 and the hsp90-binding immunophilins in signalling protein movement
Pratt, W. B., Galigniana, M. D., Harrell, J. M., & DeFranco, D. B. (2004) · Cellular Signalling · doi:10.1016/j.cellsig.2004.02.004 · Cited by 285

See all 126

Authors: Knoblauch, R., & Garabedian, M. J.
Affiliations: New York University (US)
ORCID: Garabedian, Michael J.
Venue: Molecular and Cellular Biology
Publisher: Informa UK Limited
Published: 1999-05
Volume: 19
Issue: 5
Pages: 3748-3759
ISSN: 0270-7306 (ISSN-L)
1098-5549
DOI: 10.1128/mcb.19.5.3748
PMC: PMC84199
OpenAlex: W2105740297
Cited by: 126
References: 59
Citations by year: 2026: 1 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 2 · 2020: 1 · 2019: 2 · 2018: 5 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 5
FWCI: 3.34
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Molecular and Cellular Biology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Irma T. Hirschl Trust
National Institutes of Health
National Institute of General Medical Sciences (2T32 GM-07308, T32GM007308)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: p23, estrogen receptor, HSP90, signal transduction, steroid hormone signaling, chaperone complex, immunophilins, estradiol binding, transcriptional activation, nuclear localization, MCF-7 cells
MeSH terms: Estradiol, Fluorescent Antibody Technique, Humans, Luminescent Proteins, Mutation, Nuclear Proteins, Receptors, Estrogen, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Suppression, Genetic, Tumor Cells, Cultured, Signal Transduction, Transcriptional Activation, Gene Expression Regulation, Fungal, Molecular Chaperones, HSP90 Heat-Shock Proteins, Green Fluorescent Proteins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Role for Hsp90-Associated Cochaperone p23 in Estrogen Receptor Signal Transduction

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks