ArticleOncotarget2016
Protein phosphatase 1 suppresses androgen receptor ubiquitylation and degradation.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- The crosstalk between ubiquitination and endocrine therapy.Journal of molecular medicine (Berlin, Germany) · 2023Review
- Tautomycin and enzalutamide combination yields synergistic effects on castration-resistant prostate cancer.Cell death discovery · 2022Article
- Androgen receptor splice variant 7 functions independently of the full length receptor in prostate cancer cells.Cancer letters · 2021Article
- Regulation and targeting of androgen receptor nuclear localization in castration-resistant prostate cancer.The Journal of clinical investigation · 2021Article
- Protein phosphatase 1 alpha enhances glucocorticoid receptor activity by a mechanism involving phosphorylation of serine-211.Molecular and cellular endocrinology · 2020Article
- Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer.Asian journal of urology · 2020Review
- A molecule inducing androgen receptor degradation and selectively targeting prostate cancer cells.Life science alliance · 2019Article
- Differential regulation of the androgen receptor by protein phosphatase regulatory subunits.Oncotarget · 2018Article
- Positive feedback loop mediated by protein phosphatase 1α mobilization of P-TEFb and basal CDK1 drives androgen receptor in prostate cancer.Nucleic acids research · 2017Article
- Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer.Oncotarget · 2016Review
- SKP2 E3 ligase in urological malignancies: a critical regulator of the cell cycle and therapeutic target.Cell cycle (Georgetown, Tex.)Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
The phosphoprotein phosphatases are emerging as important androgen receptor (AR) regulators in prostate cancer (PCa). We reported previously that the protein phosphatase 1 catalytic subunit (PP1α) can enhance AR activity by dephosphorylating a site in the AR hinge region (Ser650) and thereby decrease AR nuclear export. In this study we show that PP1α increases the expression of wildtype as well as an S650A mutant AR, indicating that it is acting through one or more additional mechanisms. We next show that PP1α binds primarily to the AR ligand binding domain and decreases its ubiquitylation and degradation. Moreover, we find that the PP1α inhibitor tautomycin increases phosphorylation of AR ubiquitin ligases including SKP2 and MDM2 at sites that enhance their activity, providing a mechanism by which PP1α may suppress AR degradation. Significantly, the tautomycin mediated decrease in AR expression was most pronounced at low androgen levels or in the presence of the AR antagonist enzalutamide. Consistent with this finding, the sensitivity of LNCaP and C4-2 PCa cells to tautomycin, as assessed by PSA synthesis and proliferation, was enhanced at low androgen levels or by treatment with enzalutamide. Together these results indicate that PP1α may contribute to stabilizing AR protein after androgen deprivation therapies, and that targeting PP1α or the AR-PP1α interaction may be effective in castration-resistant prostate cancer (CRPC).
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.