Glycogen Synthase Kinase-3β Is Involved in the Phosphorylation and Suppression of Androgen Receptor Activity
Open accessAbstract
Kinases can phosphorylate and regulate androgen receptor activity during prostate cancer progression. In particular, we showed that glycogen synthase kinase-3 beta phosphorylates the androgen receptor, thereby inhibiting androgen receptor-driven transcription. Conversely, the glycogen synthase kinase-3 beta inhibitor lithium chloride suppressed the glycogen synthase kinase-3 beta-mediated phosphorylation of the androgen receptor, thereby enabling androgen receptor-driven transcription to occur. The androgen receptor hinge and ligand-binding domains were important for both the phosphorylation and the inhibition of transcriptional activity of the receptor by glycogen synthase kinase-3 beta. Furthermore, androgen receptor phosphorylation was augmented by LY294002, an indirect inhibitor of protein kinase B/Akt that inhibits glycogen synthase kinase-3 beta. We also showed that the mutation of various phosphorylation sites on glycogen synthase kinase-3 beta affected the ability of these mutants to co-distribute with the androgen receptor in the cell nucleus, also that both glycogen synthase kinase-3beta and androgen receptor proteins can be found in cell nuclei of prostate cancer tissue samples. Because glycogen synthase kinase-3 beta activity is suppressed after the enzyme is phosphorylated by protein kinase B/Akt and Akt activity frequently increases during the progression of prostate cancer, nullification of the glycogen synthase kinase-3 beta-mediated suppression of androgen receptor activity by Akt likely contributes to prostate cancer progression.
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
Cites
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?
Both FOXO3a and GSK-3β modulate transcription of androgen receptor; FOXO3a promotes transcriptional activity of AR, while GSK-3β acts as its inhibitor.
“Moreover, both FOXO3a and GSK-3β modulate transcription of androgen receptor (AR); while the former promotes transcriptional activity of AR (49), the latter acts as its inhibitor (50).”
From Anabolic effect of plant brassinosteroid (2011) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The development of androgen-independent prostate cancer.
Feldman, B. J., & Feldman, D. (2001) · Nature reviews. Cancer · doi:10.1038/35094009 · Cited by 2,326 · see citing works
Cohen, P., & Frame, S. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096075 · Cited by 1,478 · see citing works
GSK3 takes centre stage more than 20 years after its discovery
FRAME, S., & COHEN, P. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3590001 · Cited by 1,433 · see citing works
Kennelly, P. J., & Krebs, E. G. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98436-x · Cited by 1,350 · see citing works
GSK3 takes centre stage more than 20 years after its discovery
Frame, S., & Cohen, P. (2001) · Biochemical Journal · doi:10.1042/bj3590001 · Cited by 997 · see citing works
Paweletz, C. P., Charboneau, L., Bichsel, V. E., Simone, N. L., Chen, T., Gillespie, J. W., Emmert‐Buck, M. R., Roth, M. J., Petricoin, E. F., & Liotta, L. A. (2001) · Oncogene · doi:10.1038/sj.onc.1204265 · Cited by 956 · see citing works
Nelson, W. G., Marzo, A. M. D., & Isaacs, W. B. (2003) · New England Journal of Medicine · doi:10.1056/nejmra021562 · Cited by 951 · see citing works
Frame, S., Cohen, P., & Biondi, R. M. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00253-2 · Cited by 703 · see citing works
Crystal Structure of Glycogen Synthase Kinase 3β
Dajani, R., Fraser, E., Roe, S. M., Young, N., Good, V. M., Dale, T. C., & Pearl, L. H. (2001) · Cell · doi:10.1016/s0092-8674(01)00374-9 · Cited by 678 · see citing works
Wen, Y., Hu, M. C. ‐., Makino, K., Spohn, B., Bartholomeusz, G. A., Yan, D., & Hung, M. (2000) · PubMed · Cited by 461 · see citing works
Jenster, G., van der Korput, H. A. G. M., Trapman, J., & Brinkmann, A. O. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7341 · Cited by 419 · see citing works
Self-citationAkt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor.
Lin, H.-K., Yeh, S., Kang, H.-Y., & Chang, C. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121173298 · Cited by 401 · see citing works
Structure of GSK3beta reveals a primed phosphorylation mechanism.
ter Haar, E., Coll, J. T., Austen, D. A., Hsiao, H.-M., Swenson, L. L., & Jain, J. (2001) · Nature Structural Biology · doi:10.1038/89624 · Cited by 394 · see citing works
Androgen Receptor Phosphorylation
Gioeli, D. G., Ficarro, S. B., Kwiek, J. J., Aaronson, D. S., Hancock, M., Catling, A. D., White, F. M., Christian, R. E., Settlage, R. E., Shabanowitz, J., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204131200 · Cited by 355 · see citing works
Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer.
Malik, S. N., Brattain, M. G., Ghosh, P., Troyer, D. A., Prihoda, T. J., Bedolla, R. G., & Kreisberg, J. I. (2002) · PubMed · Cited by 321 · see citing works
Mechanisms of androgen receptor activation and function
Brinkmann, A. O., Blok, L. J., de Ruiter, P. E., Doesburg, P., Steketee, K., Berrevoets, C., & Trapman, J. (1999) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(99)00049-7 · Cited by 308 · see citing works
Davies, M. A., Koul, D., Dhesi, H., et al. (1999) · PubMed · Cited by 276 · see citing works
Nuclear import of the human androgen receptor
Jenster, G. W., Trapman, J., & Brinkmann, A. O. (1993) · Biochemical Journal · doi:10.1042/bj2930761 · Cited by 273 · see citing works
Self-citationThe role of the androgen receptor in the development and progression of prostate cancer.
Jenster, G. W. (1999) · PubMed · Cited by 239 · see citing works
Self-citationIdentification of three proline-directed phosphorylation sites in the human androgen receptor
Zhou, Z. X., Kemppainen, J., & Wilson, E. M. (1995) · Molecular Endocrinology · doi:10.1210/mend.9.5.7565807 · Cited by 186 · see citing works
Subbarayan, V., Sabichi, A. L., Llansa, N., et al. (2001) · PubMed · Cited by 115 · see citing works
Self-citationManin, M., Baron, S., Goossens, K., Beaudoin, C., Jean, C., VEYSSIERE, G., Verhoeven, G., & Morel, L. (2002) · Biochemical Journal · doi:10.1042/bj20020585 · Cited by 107 · see citing works
Jenster, G. W., de Ruiter, P. E., van der Korput, H. A. G. M., Kuiper, G. G. J. M., Trapman, J., & Brinkmann, A. O. (1994) · Biochemistry · doi:10.1021/bi00251a015 · Cited by 104 · see citing works
Self-citationDavies, M. A., Kim, S. J., Parikh, N. U., et al. (2002) · PubMed · Cited by 96 · see citing works
A new procedure for the quantitation of nuclear and cytoplasmic androgen receptors.
TRAISH, A. M., MULLER, R. E., & Wotiz, H. H. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43228-0 · Cited by 75 · see citing works
Salas, T. R., Reddy, S. A. G., Clifford, J. L., Davis, R. J., Kikuchi, A., Lippman, S. M., & Menter, D. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302972200 · Cited by 70 · see citing works
Self-citationMurai, H., Okazaki, M., & Kikuchi, A. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00806-x · Cited by 70 · see citing works
Self-citationJenster, G. W. (2000) · The Journal of Pathology · doi:10.1002/1096-9896(200007)191:3 · Cited by 61 · see citing works
Self-citationSchilling, K., & Liao, S. (1984) · The Prostate · doi:10.1002/pros.2990050603 · Cited by 48 · see citing works
Kaufman, M., Pinsky, L., Hollander, R., et al. (1983) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(83)90055-9 · Cited by 42 · see citing works
Identification of a Novel Phosphorylation Site in Human Androgen Receptor by Mass Spectrometry
Zhu, Z., Becklin, R. R., Desiderio, D. M., & Dalton, J. T. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5030 · Cited by 32 · see citing works
The clinical and biological study of androgen independent prostate cancer (AI PCa).
Logothetis, C. J., Hoosein, N. M., & Hsieh, J. (1994) · PubMed · Cited by 31 · see citing works
Self-citationPhysicochemical characterization of the androgen receptor from hyperplastic human prostate
Murthy, L. R., Chang, C.-H., Rowley, D. R., et al. (1984) · The Prostate · doi:10.1002/pros.2990050602 · Cited by 19 · see citing works
Dubé, J. Y., Chapdelaine, P., Dionne, F. T., et al. (1978) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-47-1-41 · Cited by 6 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Lin, H. K., Yeh, S., Kang, H. Y., and Chang, C. (2001) Proc. Natl. Acad. Sci.
Cited by
Sorted by citations
Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases
Beurel, E., Grieco, S. F., & Jope, R. S. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.11.016 · Cited by 1,768 · see citing works
Heemers, H. V., & Tindall, D. J. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0019 · Cited by 753 · see citing works
Interaction of Nuclear Receptors with the Wnt/β-Catenin/Tcf Signaling Axis: Wnt You Like to Know?
Mulholland, D. J., Dedhar, S., Coetzee, G. A., & Nelson, C. C. (2005) · Endocrine Reviews · doi:10.1210/er.2003-0034 · Cited by 377 · see citing works
Roles and regulation of Wnt signaling and β-catenin in prostate cancer
Verras, M., & Sun, Z. (2006) · Cancer Letters · doi:10.1016/j.canlet.2005.06.004 · Cited by 180 · see citing works
The hinge region in androgen receptor control
Clinckemalie, L., Vanderschueren, D., Boonen, S., & Claessens, F. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.02.019 · Cited by 104 · see citing works
Androgen axis in prostate cancer.
Culig, Z., & Bartsch, G. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20898 · Cited by 102 · see citing works
Kinases and protein phosphorylation as regulators of steroid hormone action
Weigel, N. L., & Moore, N. L. (2007) · Nuclear Receptor Signaling · doi:10.1621/nrs.05005 · Cited by 72 · see citing works
Anabolic effect of plant brassinosteroid
Esposito, D., Komarnytsky, S., Shapses, S., & Raskin, I. (2011) · The FASEB Journal · doi:10.1096/fj.11-181271 · Cited by 44 · see citing works
GSK-3 inhibition sensitizes acute myeloid leukemia cells to 1,25D-mediated differentiation
Gupta, K., Stefan, T., Ignatz-Hoover, J., Moreton, S., Parizher, G., Saunthararajah, Y., & Wald, D. N. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2290 · Cited by 44 · see citing works
- Authors
- Salas, T. R., Kim, J., Vakar-Lopez, F., Sabichi, A. L., Troncoso, P., Jenster, G., Kikuchi, A., Chen, S.-Y., Shemshedini, L., Suraokar, M., Logothetis, C. J., DiGiovanni, J., Lippman, S. M., & Menter, D. G.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Erasmus MC (NL)
- Hiroshima University (JP)
- University of Toledo (US)
- Corresponding author
- Menter, David G.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 279
- Issue
- 18
- Pages
- 19191-19200
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2166599679
- Cited by
- 81
- References
- 34
- Citations by year
- 2026: 1 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 6 · 2016: 3 · 2015: 6 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 5.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA57730, R25CA57730)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- glycogen synthase kinase-3β, androgen receptor, receptor phosphorylation, androgen receptor transcriptional activity, prostate cancer progression, lithium chloride, Akt/protein kinase B, LY294002, ligand-binding domain
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Cell Compartmentation, Humans, Male, Phosphorylation, Prostatic Neoplasms, Receptors, Androgen, Transcription, Genetic, Transfection, Genetic Variation, Gene Expression Regulation, Neoplastic, Protein Structure, Tertiary, Glycogen Synthase Kinase 3, Cell Line, Tumor, Androgen Receptor Antagonists
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
