Phospho-AR (S94) Antibody

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Description

Phosphorylation of S94 in AR Function

Phosphorylation at S94 is part of a broader network of post-translational modifications (PTMs) that regulate AR activity. The N-terminal domain, where S94 is located, contains multiple phosphosites (e.g., S81, S256, Y363) that are dynamically regulated by kinases such as CDK1 and CDK9 .

PhosphositeDomainKinaseBiological Role
S94N-terminalCDK1/CDK9Transcriptional activation
S81N-terminalCDK1Protein stability
S650HingePP1Nuclear localization

Development and Validation of Phospho-AR (S94) Antibody

The antibody is typically generated using synthetic phosphopeptides corresponding to the AR S94 sequence. Key steps in its development include:

  1. Peptide Design: A 15-mer peptide containing phosphorylated S94 is conjugated to a carrier protein (e.g., KLH or BSA) for immunization .

  2. Affinity Purification: Polyclonal or monoclonal antibodies are purified to ensure specificity for phosphorylated S94 .

  3. Validation: Western blotting and immunoprecipitation confirm the antibody’s ability to distinguish phosphorylated AR from unmodified forms .

Methodological Considerations

The antibody is optimized for use in:

  • Western Blotting: Detects phosphorylated AR in lysates from prostate cancer cells (e.g., LNCaP) .

  • Immunohistochemistry: Identifies S94 phosphorylation in tumor tissues, aiding in stratifying patients for targeted therapies .

Gaps and Future Directions

  • Mechanistic Studies: The role of S94 phosphorylation in AR dimerization or chromatin binding remains unexplored.

  • Cancer Biomarker Potential: Large-scale clinical studies are needed to validate S94 as a predictive marker for androgen deprivation therapy response.

Product Specs

Buffer
Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide.
Form
Liquid
Lead Time
Typically, we can dispatch the products within 1-3 business days of receiving your order. Delivery times may vary depending on the purchasing method or location. For specific delivery details, please consult your local distributors.
Synonyms
AIS antibody; ANDR_HUMAN antibody; Androgen nuclear receptor variant 2 antibody; Androgen receptor (dihydrotestosterone receptor; testicular feminization; spinal and bulbar muscular atrophy; Kennedy disease) antibody; Androgen receptor antibody; androgen receptor splice variant 4b antibody; AR antibody; AR8 antibody; DHTR antibody; Dihydro testosterone receptor antibody; Dihydrotestosterone receptor (DHTR) antibody; Dihydrotestosterone receptor antibody; HUMARA antibody; HYSP1 antibody; KD antibody; Kennedy disease (KD) antibody; NR3C4 antibody; Nuclear receptor subfamily 3 group C member 4 (NR3C4) antibody; Nuclear receptor subfamily 3 group C member 4 antibody; SBMA antibody; SMAX1 antibody; Spinal and bulbar muscular atrophy (SBMA) antibody; Spinal and bulbar muscular atrophy antibody; Testicular Feminization (TFM) antibody; TFM antibody
Target Names
AR
Uniprot No.

Target Background

Function
Steroid hormone receptors are ligand-activated transcription factors that play a crucial role in regulating eukaryotic gene expression. They influence cellular proliferation and differentiation in target tissues. The activity of transcription factors is modulated by bound coactivator and corepressor proteins. For example, ZBTB7A recruits NCOR1 and NCOR2 to androgen response elements (ARE) on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation. Transcription activation is also down-regulated by NR0B2. The protein is activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3. Importantly, it lacks the C-terminal ligand-binding domain, which may lead to constitutive activation of a specific set of genes independently of steroid hormones.
Gene References Into Functions
  1. AR expression heterogeneity is linked to distinct castration/enzalutamide responses in castration-resistant prostate cancer. PMID: 30190514
  2. Androgen receptor positive triple negative breast cancer: Clinicopathologic, prognostic, and predictive features PMID: 29883487
  3. In prostate cancer cells, AR-V7 expression is correlated with drug resistance, as AR-V7 upregulation leads to enhanced proliferation potency of cancer cells, indicating unfavorable prognosis of patients. PMID: 30284554
  4. These findings imply that the deep intronic mutation creating an alternative splice acceptor site resulted in the production of a relatively small amount of wildtype androgen receptor mRNA, leading to partial androgen insensitivity syndrome. PMID: 29396419
  5. AR Germline Mutations and Polymorphisms were associated with Prostate Cancer. PMID: 30139231
  6. GTEE also downregulated the expression of AR and prostate-specific antigen (PSA) in both androgen-responsive and castration-resistant PCa cells. By blocking the SREBP-1/AR axis, GTEE suppressed cell growth and progressive behaviors, as well as activating the caspase-dependent apoptotic pathway in PCa cells PMID: 30301150
  7. Suppressed the expression of androgen receptor. PMID: 29981500
  8. An AR motif of the transactivation domain has been identified that contributes to transcriptional activity by recruiting the C-terminal domain of subunit 1 of the general transcription regulator TFIIF. PMID: 29225078
  9. In LNCaP prostate cancer cells, TSG101 overexpression recruits the androgen receptor (AR) to TSG101-containing cytoplasmic vesicles resulting in reduced AR protein level and AR transactivation activity downregulation. Immunofluorescence microscopy demonstrated that TSG101-decorated cytoplasmic vesicles are associated with late endosomes/lysosomes. PMID: 29859188
  10. Study indicates that both mRNA and protein level of AR increase during prostate cancer (PCa) progression. These levels are even higher in metastatic PCa. Further data suggest that elevation of AR may promote PCa metastasis by induction of EMT and reduction of KAT5. PMID: 30142696
  11. This study aimed to determine the presence and localization of oestrogen receptors (ERs), progesterone receptors (PRs), and androgen receptors (ARs) in both healthy and varicose vein wall cells and their relationship with gender. PMID: 30250632
  12. These findings suggest that CDK11 is involved in the regulation of AR pathway and AR can be a potential novel prognostic marker and therapeutic target for osteosarcoma treatment. PMID: 28262798
  13. We use CPRC prostate cancer model and demonstrate that endothelial cells secrete large amount of CCL5 and induces autophagy by suppressing AR expression in prostate cancer cell lines. Consequently, elevated autophagy accelerates focal adhesions proteins disassembly and promoted prostate cancer invasion. Inhibition of both CCL5/CCR5 signaling and autophagy significantly reduces metastasis in vivo PMID: 30200999
  14. Overexpression of nuclear AR-V7 protein identifies a subset of tumors with remarkably aggressive growth characteristics among clinically and histologically high-risk patients at the time of radical prostatectomy. PMID: 29198908
  15. Study defines AR ligand-binding domain homodimerization as an essential step in the proper functioning of this important transcription factor. Dimerization surface harbours over 40 previously unexplained androgen insensitivity syndromes and prostate cancer-associated point mutations. PMID: 28165461
  16. Loss of AR expression was found in the nucleus of penile cancer cells when compared to normal tissues. Cytoplasmic AR immunostaining was observed in a significant number of these cases and was related with poor prognosis and shorter overall survival. PMID: 30099587
  17. The AR polymorphism is associated with POR risk, patients with repeats greater than 22 show a higher risk. Our data suggest that AR genotype could play a role in natural ovarian aging. PMID: 29886316
  18. In all, these data suggest that Aurora A plays a pivotal role in regulation of Androgen receptor variant 7 expression and represents a new therapeutic target in castrate-resistant prostate cancer. PMID: 28205582
  19. The meta-analysis showed that short CAG and GGN repeats in androgen receptor gene were associated with increased risk of prostate cancer, especially in Caucasians. PMID: 28091563
  20. Knockdown of beta-Klotho produced the opposite effects. In conclusion, beta-Klotho inhibits EMT and plays a tumorsuppressive role in prostate cancer (PCa) , linking FGF/FGFR/beta-Klotho signaling to the regulation of PCa progression. PMID: 29749458
  21. The interaction of AR and SP1 contributes to regulate EPHA3 expression. PMID: 29917167
  22. DHX15 regulates androgen receptor (AR) activity by modulating E3 ligase Siah2-mediated AR ubiquitination independent of its ATPase activity promoting prostate cancer progression. PMID: 28991234
  23. The interaction of Nanog with the AR signaling axis might induce or contribute to Ovarian cancer stem cells regulation. In addition, androgen might promote stemness characteristics in ovarian cancer cells by activating the Nanog promoter PMID: 29716628
  24. a significant subset of endometrial cancers express androgen receptor especially a serous cancers. PMID: 29747687
  25. Letter: eradication of androgen receptor amplification, PSA decline, and clinical improvement with high dose testosterone therapy. PMID: 28040353
  26. The results in this meta-analysis indicated that AR CAG and GGN repeat polymorphisms may be an important pathogenesis of cryptorchidism. PMID: 29044734
  27. the inverse relation observed between bone cell activity and tumor cell AR activity in prostate cancer bone metastasis may be of importance for patient response to AR. PMID: 29670000
  28. Length variations of (CAG)n and (GGC)n polymorphism in the transactivation domain of AR, significantly influence hormonal profile, semen parameters, and sexual functions of asthenospermic subjects by down regulating the expression of AR mediating signaling. PMID: 29083935
  29. Data suggest that somatic mosaicism in AR can cause partial androgen insensitivity syndrome. [CASE REPORT] PMID: 29267169
  30. These results identify HoxB13 as a pivotal upstream regulator of AR-V7-driven transcriptomes that are often cell context-dependent in CRPC, suggesting that HoxB13 may serve as a therapeutic target for AR-V7-driven prostate tumors. PMID: 29844167
  31. TRX1 is an actionable castration-resistant prostate cancer therapeutic target through its protection against AR-induced redox stress. PMID: 29089489
  32. these findings reveal AR-genomic structural rearrangements as important drivers of persistent AR signalling in castration-resistant prostate cancer. PMID: 27897170
  33. AR+ was associated with lower breast cancer mortality in the overall study population ( estrogen receptor-negative). PMID: 28643022
  34. nuclear COBLL1 interacts with AR to enhance complex formation with CDK1 and facilitates AR phosphorylation for genomic binding in castration-resistant prostate cancer model cells. PMID: 29686105
  35. A variety of AR mutants are induced under selective pressures of AR pathway inhibition in castration resistant prostate cancer which remain sensitive to the inhibitor darolutamide. PMID: 28851578
  36. c.3864T>C AR novel mutation is responsible for complete androgen insensitivity syndrome [case report] PMID: 29206494
  37. The Spinal and bulbar muscular atrophy is caused by the expansion of a CAG/glutamine tract in the amino-terminus of the androgen receptor PMID: 29478604
  38. Polysomic AR genes show low methylation levels and high AR protein expression on immunohistochemistry PMID: 29802469
  39. Oral administration of RAD140 substantially inhibited the growth of AR/ER(+) breast cancer patient-derived xenografts (PDX). Activation of AR and suppression of ER pathway, including the ESR1 gene, were seen with RAD140 treatment. PMID: 28974548
  40. The aims of this study was to evaluate if extreme CAG and GGN repeat polymorphisms of the androgen receptors influence body fat mass, its regional distribution, resting metabolic rate, maximal fat oxidation capacity and serum leptin, free testosterone and osteocalcin in healthy adult men PMID: 29130706
  41. The CRISPR/Cas9 system was able to edit the expression of AR and restrain the growth of androgen-dependent prostate cancer cells in vitro, suggesting the potential of the CRISPR/Cas9 system in future cancer therapy. PMID: 29257308
  42. A new mechanism for complete androgen insensitivity syndrome (CAIS). A deep intronic pseudoexon-activating mutation in the intron between exons 6 and 7 of AR, detected in two siblings with CAIS, leads to aberrant splicing of the AR mRNA and insufficient AR protein production. PMID: 27609317
  43. In the current work, we have confirmed that the lead androgen receptor DBD inhibitor indeed directly interacts with the androgen receptor DBD and tested that substance across multiple clinically relevant castration-resistant prostate cancer cell lines PMID: 28775145
  44. Androgen receptor CAG repeat polymorphism is not associated with insulin resistance and type 2 diabetes in Sri Lankan males. PMID: 29202793
  45. AR gene CAG repeat polymorphisms are associated with the increased risk of mild endometriosis PMID: 28915409
  46. ARE full sites generate a reliable transcriptional outcome in AR positive cells, despite their low genome-wide abundance. In contrast, the transcriptional influence of ARE half sites can be modulated by cooperating factors. PMID: 27623747
  47. Targeting the Malat1/AR-v7 axis via Malat1-siRNA or ASC-J9 can be developed as a new therapy to better suppress enzalutamide-resistant prostate cancer progression. PMID: 28528814
  48. High circulating AR-V7 levels predicted resistance to abiraterone and enzalutamide in castration-resistant prostate cancer. PMID: 28818355
  49. Results identified the N-terminal region of AR-V7 (splice variants) that interacts with the diffuse B-cell lymphoma homology (DH) domain of Vav3 which increases its expression in castration-resistant prostate cancer (CRPC). PMID: 28811363
  50. The single nucleotide polymorphism G1733A of the androgen receptor gene is significantly associated with recurrent spontaneous abortions in Mexican patients. PMID: 28707146

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Database Links

HGNC: 644

OMIM: 300068

KEGG: hsa:367

STRING: 9606.ENSP00000363822

UniGene: Hs.76704

Involvement In Disease
Androgen insensitivity syndrome (AIS); Spinal and bulbar muscular atrophy X-linked 1 (SMAX1); Androgen insensitivity, partial (PAIS)
Protein Families
Nuclear hormone receptor family, NR3 subfamily
Subcellular Location
Nucleus. Cytoplasm.
Tissue Specificity
[Isoform 2]: Mainly expressed in heart and skeletal muscle.; [Isoform 3]: Expressed in basal and stromal cells of the prostate (at protein level).

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