Affinage

AR

Androgen receptor · UniProt P10275

Audit flag: ungrounded claim
Length
920 aa
Mass
99.2 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

AR (NR3C4) is a ligand-activated nuclear transcription factor that governs androgen-dependent gene expression programs, most prominently driving G1-S cell cycle progression in prostate cancer through induction of G1 cyclin-dependent kinase activity and inactivating phosphorylation of RB (PMID:11943742, PMID:17940184, PMID:12612376, PMID:18301781). Unlike other steroid receptors, AR's ligand-binding domain has weak intrinsic transactivation and low affinity for canonical LxxLL coactivators; productive transcription instead depends on a strong ligand-induced N-terminal/C-terminal intramolecular interaction and on coactivator recruitment to the N-terminal domain and hinge region (PMID:11943742, PMID:17940184, PMID:12612376, PMID:18612376). AR binds androgen response elements as well as non-canonical chromatin sites — including ENZ-resistance-associated sites lacking AREs and FOXA1 motifs and distinct AR-V7 cistromes enriched for half-ARE motifs — to direct context-specific transcriptional outputs (PMID:33750801, PMID:35354884). AR target genes extend to metabolic regulators such as succinate dehydrogenase subunits SDHA/SDHB, whose suppression triggers a succinate/calcium/HSP27 feedback loop that reactivates AR protein (PMID:33709547), and to microRNA-mediated programs (miR-145, miR-325) controlling tumor progression in renal and hepatocellular carcinoma (PMID:26304926, PMID:33753989). AR activity is shaped by phosphorylation (CDK9 at S81, which sets the highest-stoichiometry hormone-induced phosphorylation and controls promoter selectivity (PMID:20980437); reversal of EGF-induced Tyr534 phosphorylation by DUSP22 (PMID:31693867)) and by direct coregulator binding, including the kinase PKD1 (PMID:18602367), homeodomain factor MEIS1 which recruits NCoR/SMRT corepressors (PMID:25158280), and a cryptic EZH2 transactivation domain that recruits AR and AR-V7 to oncogenes independent of PRC2 (PMID:36300627). AR protein abundance is set by a network of E3 ligases and deubiquitinases: CHIP activated by Aurora A phosphorylation and MYLIP (counteracted by CNPY2) drive degradation, while OTUD6A (erasing K11-linked ubiquitin) and USP14 (recruited via KIF15) stabilize AR and AR-V7 (PMID:28536143, PMID:35233061, PMID:29707137, PMID:33277366). AR also undergoes membrane-associated, microtubule/KIF5B-dependent trafficking that activates HSP27 to potentiate nuclear transcription (PMID:29934310), and its mRNA is post-transcriptionally controlled by m6A (METTL3/YTHDF2, YTHDF3/G3BP1) and m5C (NSUN2/YBX1) modifications (PMID:36370857, PMID:36169095, PMID:34939643).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Established that AR is a ligand-activated transcription factor with a non-canonical coactivator-recruitment mechanism, explaining why its weak ligand-binding domain depends on the N-terminal domain for transactivation.

    Evidence Synthesis of domain mutagenesis, transactivation, and coregulator interaction studies

    PMID:11943742 PMID:12612376 PMID:17940184

    Open questions at the time
    • Does not resolve which coactivator surfaces engage the N-terminal domain
    • Mechanism of ligand selectivity by coregulators not defined
  2. 2002 Medium

    Identified PAK6 and DAX-1 as direct AR-interacting inhibitors, showing AR transcriptional output is restrained by partners acting through the hinge and the N/C interaction respectively.

    Evidence Yeast/mammalian two-hybrid, GST pull-down, Co-IP, kinase and reporter assays

    PMID:11773441 PMID:11875111

    Open questions at the time
    • PAK6 kinase substrate on AR not identified
    • Physiological significance of DAX-1 tethering in vivo unestablished
  3. 2008 Medium

    Defined AR as a master regulator of G1-S progression, linking androgen signaling to CDK-mediated RB inactivation and androgen-dependent proliferation.

    Evidence Cell cycle analysis, loss-of-function, RB phosphorylation assays in prostate cancer lines

    PMID:18301781

    Open questions at the time
    • Direct AR target genes mediating CDK activation not fully enumerated
    • Connection to specific cyclins unresolved
  4. 2008 High

    Confirmed the structural basis of AR transactivation and added PKD1 as a complex partner at the PSA promoter, refining how AR domain architecture and kinase partners tune transcription.

    Evidence Domain mutagenesis, reporter assays, Co-IP, ChIP at PSA promoter, siRNA

    PMID:18602367 PMID:18612376

    Open questions at the time
    • PKD1 phosphorylation site on AR not mapped
    • How N/C interaction couples to specific coactivators not defined
  5. 2010 High

    Pinpointed CDK9-mediated S81 phosphorylation as the dominant hormone-induced AR modification controlling promoter selectivity and growth, establishing a direct kinase-to-transcription link.

    Evidence In vitro kinase assay with MS, mutagenesis (S81A), pharmacological inhibition, stable cell lines

    PMID:20980437

    Open questions at the time
    • Downstream effectors of S81 phosphorylation incompletely defined
    • Whether S81 alters cofactor binding directly not shown
  6. 2014 Medium

    Showed MEIS1 directly represses AR by promoting NCoR/SMRT corepressor recruitment and modulating AR nuclear translocation, adding a corepressor-loading mechanism of AR control.

    Evidence Co-IP, GST pull-down, reporter assays, localization, ChIP at PSA promoter

    PMID:25158280

    Open questions at the time
    • MEIS1 interaction domain on AR not mapped
    • Genome-wide impact on AR cistrome unknown
  7. 2016 Medium

    Extended AR function beyond prostate to ER+ breast cancer (required for maximal ER chromatin binding) and revealed cell-cycle-resolved expansion of the AR cistrome including pro-metastatic targets.

    Evidence ChIP-seq, anti-androgen inhibition, proliferation and xenograft assays; cell-cycle-phased ChIP-seq

    PMID:27565181 PMID:27669432

    Open questions at the time
    • Mechanism of AR-ER chromatin cooperativity not resolved
    • How cell cycle phase redirects AR binding unclear
  8. 2017 High

    Resolved both protein-stability control (Aurora A→CHIP phosphorylation activating AR degradation) and direct N-terminal coactivator engagement (Vav3 DH domain) governing AR/AR-V7 activity.

    Evidence In vitro kinase assay, CHIP S273A mutagenesis, RNAi, ubiquitination assays; domain mutagenesis and Co-IP for Vav3

    PMID:28536143 PMID:28811363

    Open questions at the time
    • Whether CHIP-mediated degradation operates on AR-V7 not addressed
    • Vav3 effect on full-length AR cistrome unmeasured
  9. 2018 Medium

    Defined AR membrane trafficking and additional ubiquitin-pathway control, showing KIF5B-driven microtubule transport activates HSP27 signaling and CNPY2 protects AR from MYLIP-mediated degradation.

    Evidence Co-IP, GST pull-down, microtubule disruption, KIF5B knockdown, fractionation; ubiquitination and E2/E3 interaction assays

    PMID:29707137 PMID:29934310

    Open questions at the time
    • Functional output of membrane AR on specific genes not defined
    • Structural basis of MYLIP-AR recognition unknown
  10. 2020 Medium

    Uncovered KIF15-USP14 stabilization of AR/AR-V7 in a feedforward loop and DOT1L-marked enhancer control of AR/MYC, linking deubiquitination and chromatin marking to AR persistence.

    Evidence Co-IP, ubiquitination assays, ChIP for AR at KIF15 locus; ChIP-seq and DOT1L inhibition

    PMID:32814769 PMID:33277366

    Open questions at the time
    • How KIF15 promotes USP14 recruitment mechanistically unresolved
    • Generality of DOT1L feedforward loop beyond MYC unknown
  11. 2021 High

    Connected AR to metabolic and non-canonical chromatin programs: direct ARE-driven SDHA/SDHB regulation with a succinate/HSP27 reactivation loop, and acquisition of ARE/FOXA1-independent binding sites in enzalutamide-resistant CRPC.

    Evidence ChIP at SDH AREs, enzyme/calcium assays, kinase inhibition; genome-wide ChIP-seq, RNA-seq, PDX models

    PMID:33709547 PMID:33750801

    Open questions at the time
    • Determinants of non-canonical site selection incompletely defined
    • How succinate triggers calcium release mechanistically unclear
  12. 2022 High

    Established multi-layered post-transcriptional control of AR mRNA (m6A via METTL3/YTHDF2 and YTHDF3/G3BP1; m5C via NSUN2/YBX1), DUB-mediated stabilization (OTUD6A erasing K11 ubiquitin), and the EZH2 cryptic transactivation domain recruiting AR/AR-V7 to oncogenes.

    Evidence RNA m6A/m5C sequencing, RIP-qPCR, EMSA, polysome profiling, MS-based substrate ID, ubiquitin linkage analysis, ChIP-seq, PROTAC depletion

    PMID:34939643 PMID:35233061 PMID:36169095 PMID:36300627 PMID:36370857

    Open questions at the time
    • Interplay between competing RNA modifications not integrated
    • Whether these mRNA controls operate in prostate vs cardiac contexts uniformly unknown
  13. 2023 Medium

    Showed AR differentially controls Hippo effectors (YAP translation vs WWTR1 transcription) via SRF, broadening AR's reach into growth-control crosstalk.

    Evidence Translational and transcriptional reporters, SRF manipulation, anchorage-independent growth assays

    PMID:37385752

    Open questions at the time
    • Direct vs indirect AR control of YAP translation not separated
    • Physiological relevance in vivo untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse AR control layers — site-specific phosphorylation, ubiquitin/DUB balance, mRNA modification, membrane trafficking, and non-canonical cistrome reprogramming — are integrated into a unified regulatory logic across tissues remains unresolved.
  • No unified model linking modification states to cistrome selection
  • Tissue-specific weighting of these mechanisms undefined
  • Structural basis of non-canonical chromatin binding unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 4 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005886 plasma membrane 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2
Partners
DAX-1EZH2KIF5BMEIS1OTUD6APAK6PKD1VAV3

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 AR functions as a ligand-activated transcription factor; coregulators influence AR ligand selectivity, DNA binding capacity, histone modification, and recruitment of basal transcriptional machinery. The AR N-terminal domain recruits coactivators via mechanisms distinct from other steroid receptors, correlating with the low affinity of the ligand-binding domain for canonical LxxLL-bearing coactivators. Review of functional studies including domain mutagenesis, transactivation assays, coregulator interaction studies Endocrine reviews High 11943742 12612376 17940184
2002 PAK6 (p21-activated kinase 6) was cloned as an AR-interacting protein; it binds in vitro to the hinge region between the AR DNA- and ligand-binding domains without requiring ligand. PAK6 kinase activity is stimulated by AR binding. PAK6 inhibits AR transcriptional activity in transient transfection assays with episomal and integrated reporters, and is primarily cytoplasmic. Yeast two-hybrid/mammalian one-hybrid, in vitro binding assay, transient transfection reporter assay, in vitro kinase assay, subcellular localization by epitope tagging Molecular endocrinology Medium 11773441
2002 DAX-1 (NROB1) directly interacts with AR and potently inhibits ligand-dependent AR transcriptional activation as well as the AR N-terminal/C-terminal (N/C) domain interaction. The interaction involves the N-terminal repeat domain of DAX-1 and the C-terminal ligand-binding/activation domain of AR. DAX-1 can relocalize AR in both cytoplasm and nucleus, suggesting intracellular tethering contributes to inhibition. Co-immunoprecipitation, GST pull-down, transactivation reporter assay, subcellular localization imaging Molecular endocrinology Medium 11875111
2008 AR acts as a master regulator of G1-S phase progression in prostate cancer cells, inducing signals that promote G1 cyclin-dependent kinase (CDK) activity, leading to phosphorylation and inactivation of the retinoblastoma tumor suppressor (RB), thereby governing androgen-dependent proliferation. Cell cycle analysis, loss-of-function experiments, phosphorylation assays for RB in prostate cancer cell lines Nuclear receptor signaling Medium 18301781
2008 The AR ligand-binding domain has low intrinsic transactivation properties correlating with low affinity for canonical LxxLL-bearing coactivators; instead, AR transcriptional activation involves alternative recruitment of coactivators to the N-terminal domain and hinge region. A strong ligand-induced N-terminal/C-terminal (N/C) intramolecular interaction is involved in many aspects of AR function as a transcription factor. Domain mutagenesis, transactivation reporter assays, interaction studies with LxxLL coactivators Nuclear receptor signaling High 18612376
2008 Protein kinase D1 (PKD1) forms a protein complex with AR in prostate cancer cells and is associated with the AR transcriptional complex at the PSA gene promoter. Both wild-type and kinase-dead PKD1 attenuate ligand-dependent AR transcriptional activation, while PKD1 knockdown enhances it. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP) at PSA promoter, transactivation reporter assay, siRNA knockdown Biochemical and biophysical research communications Medium 18602367
2010 CDK9 phosphorylates AR at serine 81 (S81) in vitro and in cells; this is the highest stoichiometric phosphorylation on AR in response to hormone. CDK9 knockdown or pharmacological inhibition reduces S81 phosphorylation and AR transcriptional activity. Loss of S81 phosphorylation (S81A mutant) limits prostate cancer cell growth and alters AR promoter selectivity for endogenous target genes. In vitro kinase assay with mass spectrometry, siRNA knockdown, pharmacological inhibition (DRB, Flavopiridol), stable cell lines with wild-type vs. S81A mutant AR, endogenous target gene expression analysis Molecular endocrinology High 20980437
2006 Hic-5/ARA55 functions as a prostate stroma-specific AR coactivator; its expression influences androgen-induced keratinocyte growth factor (KGF) expression in WPMY-1 prostate stromal cells. Expression analysis in stromal vs. epithelial cells, functional transcription assay for KGF induction Steroids Low 17166536
2016 AR is required for maximum ER genomic binding in ER+/AR+ breast cancer cells; estradiol induces AR chromatin binding at sites enriched for estrogen response elements that overlap with ER-binding sites. AR inhibition (enzalutamide, MJC13) reduces baseline and estradiol-mediated proliferation and synergizes with tamoxifen and fulvestrant. ChIP-seq for AR chromatin binding, anti-androgen inhibition (enzalutamide/MJC13), cell proliferation assays, in vivo xenograft models Molecular cancer research Medium 27565181
2018 AR membrane transport to the plasma membrane is microtubule-dependent and mediated by the motor protein KIF5B; disruption of KIF5B function interferes with AR membrane association. AR physically interacts with KIF5B, and androgen enhances this interaction. Membrane-associated AR activates HSP27, which mediates membrane-to-nuclear signal transduction to potentiate nuclear AR transcriptional activity. Co-immunoprecipitation, GST pull-down, microtubule disruption assays, KIF5B knockdown, subcellular fractionation, HSP27 functional assays The Journal of biological chemistry Medium 29934310
2019 AKR1C3 increases AR-V7 protein stability in enzalutamide-resistant prostate cancer cells through activation of the ubiquitin-mediated proteasome pathway; indomethacin (AKR1C3 inhibitor) decreases AR/AR-V7 protein expression in vitro and in vivo via ubiquitin-proteasome pathway activation. Western blot protein stability assay, ubiquitin assay, pharmacological inhibition with indomethacin, in vivo xenograft model Molecular cancer therapeutics Medium 31308078
2017 Aurora kinase A (AURKA) phosphorylates the E3 ligase CHIP at S273, activating its E3 ligase activity toward AR. The 2-methoxyestradiol→Aurora A→CHIP→AR pathway promotes proteasomal degradation of AR; cells expressing CHIP S273A mutant show attenuated AR degradation, confirming this phosphorylation is required. In vitro kinase assay, site-directed mutagenesis (CHIP S273A), AURKA inhibitors and RNAi knockdown, AR ubiquitination and degradation assays Molecular cancer research High 28536143
2020 KIF15 directly binds the N-terminus of AR/AR-V7 and prevents AR/AR-V7 protein degradation by increasing the association of deubiquitinase USP14 with AR/AR-V7; in turn, transcriptionally active AR stimulates KIF15 expression, forming a reciprocal activation loop. Co-immunoprecipitation, direct binding assay, protein stability assay, ubiquitination assay, ChIP for AR at KIF15 locus Cancer research Medium 33277366
2020 DOT1L histone methyltransferase marks a distal enhancer in the MYC gene with H3K79 methylation; this enhancer is bound by AR and DOT1L specifically in AR-positive prostate cancer cells. DOT1L inhibition reduces MYC expression, upregulates E3 ubiquitin ligases HECTD4 and MYCBP2, and promotes AR and MYC degradation in a negative feedforward loop. ChIP-seq, genetic and chemical inhibition of DOT1L, AR-positive vs. AR-negative cell comparison, ubiquitin ligase expression analysis Nature communications Medium 32814769
2021 A cryptic transactivation domain of EZH2 (EZH2TAD) directly binds both AR and constitutively active AR splice variant AR-V7, mediating assembly and recruitment of transactivation-related machineries at genomic sites that lack PRC2 binding (non-canonical EZH2 function). EZH2TAD is required for chromatin recruitment of EZH2 to oncogenes and for EZH2-mediated oncogene activation in prostate cancer. Co-immunoprecipitation, ChIP-seq, domain mutagenesis, PROTAC depletion (MS177), in vitro and in vivo functional assays Nucleic acids research High 36300627
2022 METTL3 epigenetically represses AR expression in cardiac fibroblasts via m6A modification of AR mRNA in an m6A-YTHDF2-dependent manner; decreased AR expression activates HIF-1α signaling, enhancing glycolysis and cardiac fibroblast proliferation. AR interacts with HIF-1α and its overexpression reduces HIF-1α axis and inhibits glycolysis. RNA m6A sequencing, METTL3 knockdown/overexpression, Co-IP for AR-HIF-1α interaction, glycolysis assays, in vivo cardiac fibrosis model International journal of biological macromolecules Medium 36370857
2022 NSUN2 posttranscriptionally stabilizes AR mRNA through cluster m5C modification in a m5C-YBX1-dependent manner; NSUN2 depletion decreases AR and AR-V7 expression and activity. AR transcriptionally regulates NSUN2, forming a positive feedback loop. YBX1 binds to AR m5C sites as confirmed by RIP-qPCR and EMSA. RNA bisulfite sequencing (RNA-BisSeq), in vitro enzyme reaction assay, RIP-qPCR, EMSA, ChIP, luciferase assay for AR binding to NSUN2 promoter Clinical and translational medicine Medium 36169095
2022 AR mRNA translation is coordinately regulated by RNA-binding proteins YTHDF3 and G3BP1: m6A-modified AR mRNA is bound by YTHDF3 and translationally stimulated under ambient conditions, while m6A-unmodified AR mRNA is bound by G3BP1 and translationally repressed. Under AR pathway inhibition stress, m6A-modified AR mRNA recruits to stress granules (SGs) where it undergoes liquid-liquid phase separation with YTHDF3, reducing translation. Polysome profiling, RNA-protein interaction assay, stress granule imaging, m6A sequencing, YTHDF3/G3BP1 silencing Nucleic acids research Medium 34939643
2021 ENZ-resistant CRPC cells acquire non-canonical AR binding sites (ARBS-gained) lacking canonical androgen response elements (ARE) and FOXA1 motifs, which are enriched with CpG islands and binding sites for CXXC5 and TET2. ARBS-gained loci are enriched with H3K27ac, and ENZ-resistant cells are hypersensitive to BET/CBP-p300 dual inhibition. Genome-wide ChIP-seq, RNA-seq, patient-derived xenografts, pharmacological inhibition with NEO2734 Nature communications Medium 33750801
2022 OTUD6A deubiquitinase stabilizes AR by erasing K11-linked polyubiquitination of AR; catalytically inactive OTUD6A mutant fails to stabilize AR. OTUD6A also stabilizes Brg1 (SWI/SNF ATPase subunit) by erasing K27-linked polyubiquitination. Mass spectrometry substrate identification, Co-immunoprecipitation, ubiquitination assays with linkage-specific analysis, catalytically inactive mutant, in vivo xenograft models Communications biology High 35233061
2018 CNPY2 controls AR protein levels by inhibiting MYLIP (an E3 ubiquitin ligase)-mediated AR ubiquitination and proteasomal degradation; CNPY2 decreases MYLIP ubiquitination activity by inhibiting the interaction between MYLIP and E2 ubiquitin ligase UBE2D1. Ubiquitination assay, Co-immunoprecipitation, CNPY2 knockdown/overexpression, proteasome inhibitor treatment Oncotarget Medium 29707137
2021 AR directly regulates transcription of succinate dehydrogenase catalytic subunit genes (SDHA, SDHB) via androgen response elements (AREs). AR pathway inhibition suppresses SDH activity, causing succinate accumulation; succinate triggers calcium release, which phospho-activates HSP27 via CaMKK2/AMPK/p38 axis, stabilizing and reactivating AR protein. ChIP for AR at SDHA/SDHB AREs, SDH enzyme activity assay, calcium imaging, pharmacological kinase inhibition, AR protein stability assay, tissue microarray validation EMBO molecular medicine High 33709547
2014 MEIS1 homeodomain transcription factor directly interacts with AR (identified by Co-IP and GST pull-down) and inhibits AR transcriptional activity, reduces AR target gene expression, modulates AR cytoplasm/nucleus translocation, and promotes recruitment of corepressors NCoR and SMRT to the AR complex in the presence of androgen. Co-immunoprecipitation, GST pull-down, transactivation reporter assay, subcellular localization assay, ChIP for AR at PSA promoter Experimental cell research Medium 25158280
2019 DUSP22 interacts with AR as a regulatory partner, dephosphorylates AR at Tyr534 to interfere with EGF-induced AR phosphorylation, and suppresses PSA gene expression through phosphatase-dependent pathways. DUSP22 also dephosphorylates EGFR and its downstream ERK1/2 signaling. Co-immunoprecipitation, phosphorylation assay (Tyr534 AR), DUSP22 overexpression/loss-of-function, PSA reporter assay FASEB journal Medium 31693867
2016 AR has an expanded repertoire of transcriptional targets in actively cycling prostate cancer cells, segregating into cell-cycle-common and phase-restricted AR functions. AR regulates dihydroceramide desaturase 1 specifically in mitotically active cells, promoting pro-metastatic phenotypes. AR ChIP-seq as a function of cell cycle phase, gene expression profiling, functional assays for pro-metastatic phenotypes Oncogene Medium 27669432
2022 AR-EZH2 protein interaction is impaired by pre-castration androgen levels but recovered by post-castration androgen levels; AR overexpression alone with low androgen can rapidly redistribute AR chromatin binding and activate a distinct transcription program enriched for DNA damage repair pathways, with EZH2 involvement in this reprogramming. Co-IP for AR-EZH2 interaction, inducible AR overexpression model, ChIP-seq cistrome analysis, RNA-seq, bioinformatic prediction Frontiers in oncology Medium 36408179
2023 AR activates YAP translation and induces transcription of the TAZ-encoding gene WWTR1 in prostate cancer, differentially regulating these two Hippo pathway effectors. AR-mediated YAP/TAZ activation is regulated by the RhoA transcriptional mediator SRF. YAP/TAZ are not essential for sustaining AR activity. Androgen stimulation, AR inhibition, translational reporter assay, transcription assay, SRF manipulation, anchorage-independent growth assays Life science alliance Medium 37385752
2017 Vav3 DH domain directly interacts with the N-terminal region of AR-V7 (and full-length AR); Vav3 DH domain expression disrupts Vav3-AR-V7 interaction and inhibits Vav3 enhancement of AR-V7 activity, also disrupting AR-V7 interaction with coactivators SRC1 and Vav2. Disruption of AR-V7/coactivator interaction decreases AR-V7 nuclear levels. Mutational and biochemical domain interaction studies, Co-IP, transcriptional reporter assays, functional cell proliferation and anchorage-independent growth assays Molecular cancer research Medium 28811363
2020 ACK1 (oncogenic tyrosine kinase) phosphorylates histone H4, leading to epigenetic upregulation of AR expression as a mechanism of castration-resistant prostate cancer resistance to anti-androgens. Kinase assay, chromatin analysis of H4 phosphorylation at AR locus, ACK1-selective inhibitor (R)-9b NAR cancer Low 32885168
2022 AR-V7 and full-length AR display distinct cistromes with numerous differential chromatin binding sites in prostate cancer cells; AR-V7 preferential binding sites are enriched for a half-ARE de novo motif and are located proximal to transcription start sites, without FOXA1 enrichment, distinguishing them from canonical half-ARE AR-V7 sites. ChIP-seq for AR and AR-V7 at matched expression levels in LNCaP and VCaP cells, de novo motif analysis, RNA-seq transcriptome comparison Scientific reports Medium 35354884
2015 AR binds to androgen response elements (AREs) in the miR-145 promoter and suppresses p53-induced miR-145 expression; decreased miR-145 leads to upregulation of HIF2α/VEGF/MMP9/CCND1 in renal cell carcinoma, promoting tumor progression independent of VHL status. ChIP for AR at miR-145 promoter ARE, luciferase reporter assay, AR-shRNA knockdown, miR-145 mimic rescue, orthotopic xenograft mouse model Oncotarget Medium 26304926
2021 AR directly regulates HCC cell migration and invasion via a miR-325/ACP5 signaling axis; AR transcriptionally regulates miR-325, which directly targets the 3'UTR of ACP5 mRNA to suppress its translation and reduce cell migration/invasion. AR knockdown, miR-325 overexpression, 3'UTR luciferase reporter assay for ACP5, in vivo orthotopic xenograft model Journal of Cancer Medium 33753989
2018 CpG methylation of the proximal AR promoter inversely correlates with AR mRNA expression; a 158-bp region containing two consecutive CpGs is sufficient to suppress reporter gene expression when methylated. RUNX1 binds this region and ectopic RUNX1 expression inhibits reporter gene expression through this region, identifying it as a regulator of AR transcription. Bisulfite sequencing of AR promoter, luciferase reporter assay with methylated template, RUNX1 ChIP and ectopic expression in HEK293T cells The Journal of clinical endocrinology and metabolism Medium 30124873
2020 Sex-associated expression analysis in lungs showed that ACE2 and AR expression are sexually dimorphic and higher in males; ACE2 expression is moderately suppressible by enzalutamide (AR antagonist) in male mice. TMPRSS2 expression in lungs was not increased in males vs. females and was not decreased by enzalutamide treatment (negative result for TMPRSS2-AR regulation in lung). Comparative gene expression in human and mouse lungs, pharmacological AR antagonism with enzalutamide in male mice bioRxivpreprint Low 33083800

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Androgen receptor (AR) coregulators: an overview. Endocrine reviews 707 11943742
2007 Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocrine reviews 573 17940184
2000 AIS is an oncogene amplified in squamous cell carcinoma. Proceedings of the National Academy of Sciences of the United States of America 422 10805802
2015 Plasma AR and abiraterone-resistant prostate cancer. Science translational medicine 390 26537258
2008 AR, the cell cycle, and prostate cancer. Nuclear receptor signaling 270 18301781
2013 Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver. Oncogene 180 23873027
1998 Development of a highly polymorphic STR marker for identity testing purposes at the human androgen receptor gene (HUMARA). Journal of forensic sciences 179 9729823
2008 Diverse roles of androgen receptor (AR) domains in AR-mediated signaling. Nuclear receptor signaling 176 18612376
2017 AR Signaling and the PI3K Pathway in Prostate Cancer. Cancers 140 28420128
2012 Androgen receptor (AR) aberrations in castration-resistant prostate cancer. Molecular and cellular endocrinology 135 22245783
2016 Cooperative Dynamics of AR and ER Activity in Breast Cancer. Molecular cancer research : MCR 116 27565181
2018 Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nature communications 115 30190514
2019 Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask). Cells 114 30995798
2010 CDK9 regulates AR promoter selectivity and cell growth through serine 81 phosphorylation. Molecular endocrinology (Baltimore, Md.) 114 20980437
2002 AR and ER interaction with a p21-activated kinase (PAK6). Molecular endocrinology (Baltimore, Md.) 114 11773441
2002 Inhibition of androgen receptor (AR) function by the reproductive orphan nuclear receptor DAX-1. Molecular endocrinology (Baltimore, Md.) 113 11875111
2013 Androgen receptor (AR) physiological roles in male and female reproductive systems: lessons learned from AR-knockout mice lacking AR in selective cells. Biology of reproduction 111 23782840
2021 Androgen receptor (AR) heterogeneity in prostate cancer and therapy resistance. Cancer letters 110 34118355
2020 Binding pathway determines norepinephrine selectivity for the human β1AR over β2AR. Cell research 109 33093660
2013 Androgen receptor (AR) positive vs negative roles in prostate cancer cell deaths including apoptosis, anoikis, entosis, necrosis and autophagic cell death. Cancer treatment reviews 102 23993415
2023 Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer. Nature cancer 98 37038004
2020 The negative regulator SMAX1 controls mycorrhizal symbiosis and strigolactone biosynthesis in rice. Nature communications 94 32355217
2020 Structure-Function Analysis of SMAX1 Reveals Domains That Mediate Its Karrikin-Induced Proteolysis and Interaction with the Receptor KAI2. The Plant cell 94 32434855
2017 AR Signaling in Breast Cancer. Cancers 94 28245550
2020 Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer. Nature communications 91 32814769
2014 Androgen receptor (AR) expression in 400 breast carcinomas: is routine AR assessment justified? American journal of cancer research 88 25057438
2021 A noncanonical AR addiction drives enzalutamide resistance in prostate cancer. Nature communications 84 33750801
2003 Resolution of clonal origins for endometriotic lesions using laser capture microdissection and the human androgen receptor (HUMARA) assay. Fertility and sterility 84 12620481
2020 KIF15-Mediated Stabilization of AR and AR-V7 Contributes to Enzalutamide Resistance in Prostate Cancer. Cancer research 77 33277366
2015 β2-AR signaling controls trastuzumab resistance-dependent pathway. Oncogene 76 25798840
2018 AR Expression in Breast Cancer CTCs Associates with Bone Metastases. Molecular cancer research : MCR 69 29453314
2014 AR function in promoting metastatic prostate cancer. Cancer metastasis reviews 69 24425228
2020 Analysis of β2AR-Gs and β2AR-Gi complex formation by NMR spectroscopy. Proceedings of the National Academy of Sciences of the United States of America 68 32868434
2013 Androgen receptor (AR) pathophysiological roles in androgen-related diseases in skin, bone/muscle, metabolic syndrome and neuron/immune systems: lessons learned from mice lacking AR in specific cells. Nuclear receptor signaling 68 24653668
2019 AKR1C3 Promotes AR-V7 Protein Stabilization and Confers Resistance to AR-Targeted Therapies in Advanced Prostate Cancer. Molecular cancer therapeutics 63 31308078
2016 Androgen receptor (AR) in cardiovascular diseases. The Journal of endocrinology 63 26769913
2022 The strigolactone receptor D14 targets SMAX1 for degradation in response to GR24 treatment and osmotic stress. Plant communications 56 35529949
1996 Quantification of X-chromosome inactivation patterns in haematological samples using the DNA PCR-based HUMARA assay. Leukemia 55 8637249
2020 The karrikin signaling regulator SMAX1 controls Lotus japonicus root and root hair development by suppressing ethylene biosynthesis. Proceedings of the National Academy of Sciences of the United States of America 52 32817510
2016 Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer. Hormones & cancer 52 26728473
2022 Positive epigenetic regulation loop between AR and NSUN2 promotes prostate cancer progression. Clinical and translational medicine 51 36169095
2017 AR-Signaling in Human Malignancies: Prostate Cancer and Beyond. Cancers 51 28085048
2016 Identification of an AR Mutation-Negative Class of Androgen Insensitivity by Determining Endogenous AR Activity. The Journal of clinical endocrinology and metabolism 51 27583472
2021 AR Splicing Variants and Resistance to AR Targeting Agents. Cancers 49 34071114
2023 Discovery of ARD-1676 as a Highly Potent and Orally Efficacious AR PROTAC Degrader with a Broad Activity against AR Mutants for the Treatment of AR + Human Prostate Cancer. Journal of medicinal chemistry 48 37683104
2018 Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand binding domain. Medicinal research reviews 48 30565725
2021 AR-V7 in Metastatic Prostate Cancer: A Strategy beyond Redemption. International journal of molecular sciences 45 34073713
2014 The transcriptional programme of the androgen receptor (AR) in prostate cancer. BJU international 42 24053777
2021 LncRNA PCBP1-AS1-mediated AR/AR-V7 deubiquitination enhances prostate cancer enzalutamide resistance. Cell death & disease 41 34545063
2001 The androgen receptor (AR) in syndromes of androgen insensitivity and in prostate cancer. The Journal of steroid biochemistry and molecular biology 41 11384871
2022 A cryptic transactivation domain of EZH2 binds AR and AR's splice variant, promoting oncogene activation and tumorous transformation. Nucleic acids research 40 36300627
2022 METTL3 boosts glycolysis and cardiac fibroblast proliferation by increasing AR methylation. International journal of biological macromolecules 40 36370857
1997 Clonal X-inactivation analysis of human tumours using the human androgen receptor gene (HUMARA) polymorphism: a non-radioactive and semiquantitative strategy applicable to fresh and archival tissue. Molecular and cellular probes 40 9232621
2022 Regulation of AR mRNA translation in response to acute AR pathway inhibition. Nucleic acids research 37 34939643
2015 Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status. Oncotarget 37 26304926
2016 Cell cycle-coupled expansion of AR activity promotes cancer progression. Oncogene 36 27669432
2020 Therapeutic targeting of the androgen receptor (AR) and AR variants in prostate cancer. Asian journal of urology 35 32742927
2024 ALDH1A1 drives prostate cancer metastases and radioresistance by interplay with AR- and RAR-dependent transcription. Theranostics 34 38169509
2000 Clonality analysis by methylation-specific PCR for the human androgen-receptor gene (HUMARA-MSP). Leukemia 32 10637497
2020 ACK1-AR and AR-HOXB13 signaling axes: epigenetic regulation of lethal prostate cancers. NAR cancer 31 32885168
2018 Membrane-associated androgen receptor (AR) potentiates its transcriptional activities by activating heat shock protein 27 (HSP27). The Journal of biological chemistry 31 29934310
2019 Adiponectin regulates bone mass in AIS osteopenia via RANKL/OPG and IL6 pathway. Journal of translational medicine 30 30819183
2000 Molecular evidence that the stromal and epithelial cells in pleomorphic adenomas of salivary gland arise from the same origin: clonal analysis using human androgen receptor gene (HUMARA) assay. Human pathology 30 10821498
2013 Cholesterol-β1 AR interaction versus cholesterol-β2 AR interaction. Proteins 29 24265091
2018 ONC201 Targets AR and AR-V7 Signaling, Reduces PSA, and Synergizes with Everolimus in Prostate Cancer. Molecular cancer research : MCR 28 29588330
2017 Aurora Kinase A Promotes AR Degradation via the E3 Ligase CHIP. Molecular cancer research : MCR 28 28536143
2008 Protein kinase D1 (PKD1) influences androgen receptor (AR) function in prostate cancer cells. Biochemical and biophysical research communications 28 18602367
2020 Sex, androgens and regulation of pulmonary AR, TMPRSS2 and ACE2. bioRxiv : the preprint server for biology 27 33083800
2017 The celecoxib derivatives AR-12 and AR-14 induce autophagy and clear prion-infected cells from prions. Scientific reports 27 29242534
2014 Association study of ERβ, AR, and CYP19A1 genes and MtF transsexualism. The journal of sexual medicine 27 25124466
2022 Cistrome and transcriptome analysis identifies unique androgen receptor (AR) and AR-V7 splice variant chromatin binding and transcriptional activities. Scientific reports 26 35354884
2021 Chemical Degradation of Androgen Receptor (AR) Using Bicalutamide Analog-Thalidomide PROTACs. Molecules (Basel, Switzerland) 26 33926033
2023 The potential therapeutic effect of phosphodiesterase 5 inhibitors in the acute ischemic stroke (AIS). Molecular and cellular biochemistry 25 37395897
2021 Targeting KDM4A-AS1 represses AR/AR-Vs deubiquitination and enhances enzalutamide response in CRPC. Oncogene 24 34759344
2014 MEIS1 functions as a potential AR negative regulator. Experimental cell research 24 25158280
2019 Revisiting the relationships of 2D:4D with androgen receptor (AR) gene and current testosterone levels: Replication study and meta-analyses. Journal of neuroscience research 23 31359506
2018 Epigenetic Repression of Androgen Receptor Transcription in Mutation-Negative Androgen Insensitivity Syndrome (AIS Type II). The Journal of clinical endocrinology and metabolism 23 30124873
2022 OTUD6A promotes prostate tumorigenesis via deubiquitinating Brg1 and AR. Communications biology 22 35233061
2022 SMAX1 potentiates phytochrome B-mediated hypocotyl thermomorphogenesis. The Plant cell 22 35478037
2020 Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis. Journal of orthopaedic surgery and research 22 33121521
2001 Where do selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) now fit into breast cancer treatment algorithms? The Journal of steroid biochemistry and molecular biology 22 11850229
2019 Non-nuclear AR Signaling in Prostate Cancer. Frontiers in chemistry 21 31616657
2019 DUSP22 suppresses prostate cancer proliferation by targeting the EGFR-AR axis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 21 31693867
2018 HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis. Ginekologia polska 21 29664547
2006 Hic-5/ARA55: a prostate stroma-specific AR coactivator. Steroids 21 17166536
2021 Huaier Extract Inhibits Prostate Cancer Growth via Targeting AR/AR-V7 Pathway. Frontiers in oncology 20 33708629
2018 AR Signaling in Human Malignancies: Prostate Cancer and Beyond. Cancers 19 29346310
2018 CNPY2 inhibits MYLIP-mediated AR protein degradation in prostate cancer cells. Oncotarget 19 29707137
2017 Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities. Molecular cancer research : MCR 19 28811363
2024 Capsaicin induces ATP-dependent thermogenesis via the activation of TRPV1/β3-AR/α1-AR in 3T3-L1 adipocytes and mouse model. Archives of biochemistry and biophysics 18 38531438
2022 Increased AR expression in castration-resistant prostate cancer rapidly induces AR signaling reprogramming with the collaboration of EZH2. Frontiers in oncology 17 36408179
2017 Androgen receptor (AR) cistrome in prostate differentiation and cancer progression. American journal of clinical and experimental urology 17 29181434
2021 Androgen receptor (AR) decreases HCC cells migration and invasion via miR-325/ACP5 signaling. Journal of Cancer 16 33753989
2020 Coordinated AR and microRNA regulation in prostate cancer. Asian journal of urology 16 32742925
2015 Multicentric occurrence of multiple papillary thyroid carcinomas--HUMARA and BRAF mutation analysis. Cancer medicine 16 25882744
2007 Association between CCK-AR gene and schizophrenia with auditory hallucinations. Psychiatric genetics 16 17413443
2023 AR activates YAP/TAZ differentially in prostate cancer. Life science alliance 15 37385752
2001 Clonality analysis using X-chromosome inactivation patterns by HUMARA-PCR assay in female controls and patients with idiopathic thrombocytosis in Taiwan. Experimental hematology 15 11166459
2021 Androgen receptor (AR) antagonism triggers acute succinate-mediated adaptive responses to reactivate AR signaling. EMBO molecular medicine 14 33709547
2025 Ethylene promotes SMAX1 accumulation to inhibit arbuscular mycorrhiza symbiosis. Nature communications 13 40016206

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