Categories
Prostate cancer

Celastrol recruits UBE3A to recognize and degrade the DNA binding domain of steroid receptors

  • Groner AC, Brown M. Role of steroid receptor and coregulator mutations in hormone-dependent cancers. J Clin Investig. 2017;127:1126–35.

    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Tata JR. Signalling through nuclear receptors. Nat Rev Mol Cell Biol. 2002;3:702–10.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Chen Y, Sawyers CL, Scher HI. Targeting the androgen receptor pathway in prostate cancer. Curr Opin Pharmacol. 2008;8:440–8.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Furr BJ. The development of Casodex (bicalutamide): preclinical studies. Eur Urol. 1996;29:83–95. Suppl 2

    PubMed 
    Article 

    Google Scholar
     

  • Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N. Engl J Med. 2012;367:1187–97.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N. Engl J Med. 2014;371:424–33.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA, Arora V, et al. Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009;324:787–90.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Antonarakis ES, Lu C, Wang H, Luber B, Nakazawa M, Roeser JC, et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N. Engl J Med. 2014;371:1028–38.

    PubMed 
    PubMed Central 
    Article 
    CAS 

    Google Scholar
     

  • Dehm SM, Schmidt LJ, Heemers HV, Vessella RL, Tindall DJ. Splicing of a novel androgen receptor exon generates a constitutively active androgen receptor that mediates prostate cancer therapy resistance. Cancer Res. 2008;68:5469–77.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, et al. Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell 2013;155:1309–22.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Efstathiou E, Titus M, Wen S, Hoang A, Karlou M, Ashe R, et al. Molecular characterization of enzalutamide-treated bone metastatic castration-resistant prostate cancer. Eur Urol. 2015;67:53–60.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Li J, Berk M, Alyamani M, Sabharwal N, Goins C, Alvarado J, et al. Hexose-6-phosphate dehydrogenase blockade reverses prostate cancer drug resistance in xenograft models by glucocorticoid inactivation. Sci Translational Med. 2021;13:eabe8226.

  • Hou Z, Huang S, Li Z. Androgens in prostate cancer: A tale that never ends. Cancer Lett. 2021;516:1–12.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Schneekloth AR, Pucheault M, Tae HS, Crews CM. Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics. Bioorg Med Chem Lett. 2008;18:5904–8.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Toure M, Crews CM. Small-Molecule PROTACS: New Approaches to Protein Degradation. Angew Chem. 2016;55:1966–73.

    CAS 
    Article 

    Google Scholar
     

  • Takwale AD, Jo SH, Jeon YU, Kim HS, Shin CH, Lee HK, et al. Design and characterization of cereblon-mediated androgen receptor proteolysis-targeting chimeras. Eur J Med Chem. 2020;208:112769.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Zhao L, Han X, Lu J, McEachern D, Wang S. A highly potent PROTAC androgen receptor (AR) degrader ARD-61 effectively inhibits AR-positive breast cancer cell growth in vitro and tumor growth in vivo. Neoplasia 2020;22:522–32.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Han X, Wang C, Qin C, Xiang W, Fernandez-Salas E, Yang CY, et al. Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer. J Med Chem. 2019;62:941–64.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Alyamani M, Li Z, Berk M, Li J, Tang J, Upadhyay S, et al. Steroidogenic Metabolism of Galeterone Reveals a Diversity of Biochemical Activities. Cell Chem Biol. 2017;24:825–32. e6

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Ponnusamy S, He Y, Hwang DJ, Thiyagarajan T, Houtman R, Bocharova V, et al. Orally Bioavailable Androgen Receptor Degrader, Potential Next-Generation Therapeutic for Enzalutamide-Resistant Prostate Cancer. Clin Cancer Res: Off J Am Assoc Cancer Res. 2019;25:6764–80.

    CAS 
    Article 

    Google Scholar
     

  • Yang Z, Chang YJ, Yu IC, Yeh S, Wu CC, Miyamoto H, et al. ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. Nat Med. 2007;13:348–53.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Hieronymus H, Lamb J, Ross KN, Peng XP, Clement C, Rodina A, et al. Gene expression signature-based chemical genomic prediction identifies a novel class of HSP90 pathway modulators. Cancer cell. 2006;10:321–30.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Yang H, Chen D, Cui QC, Yuan X, Dou QP. Celastrol, a triterpene extracted from the Chinese “Thunder of God Vine,” is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Cancer Res. 2006;66:4758–65.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Chadli A, Felts SJ, Wang Q, Sullivan WP, Botuyan MV, Fauq A, et al. Celastrol inhibits Hsp90 chaperoning of steroid receptors by inducing fibrillization of the Co-chaperone p23. J Biol Chem 2010;285:4224–31.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Scheffner M, Huibregtse JM, Vierstra RD, Howley PM. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 1993;75:495–505.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Huibregtse JM, Scheffner M, Howley PM. Cloning and expression of the cDNA for E6-AP, a protein that mediates the interaction of the human papillomavirus E6 oncoprotein with p53. Mol Cell Biol 1993;13:775–84.

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fang M, Li Y, Ren J, Hu R, Gao X, Chen L. Epilepsy-Associated UBE3A Deficiency Downregulates Retinoic Acid Signalling Pathway. Front Genet. 2021;12:681295.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Nawaz Z, Lonard DM, Smith CL, Lev-Lehman E, Tsai SY, Tsai MJ, et al. The Angelman syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily. Mol Cell Biol. 1999;19:1182–9.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Khan OY, Fu G, Ismail A, Srinivasan S, Cao X, Tu Y, et al. Multifunction steroid receptor coactivator, E6-associated protein, is involved in development of the prostate gland. Mol Endocrinol. 2006;20:544–59.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Birch SE, Kench JG, Takano E, Chan P, Chan AL, Chiam K, et al. Expression of E6AP and PML predicts for prostate cancer progression and cancer-specific death. Ann Oncol: Off J Eur Soc Med Oncol. 2014;25:2392–7.

    CAS 
    Article 

    Google Scholar
     

  • Smith CL, DeVera DG, Lamb DJ, Nawaz Z, Jiang YH, Beaudet AL, et al. Genetic ablation of the steroid receptor coactivator-ubiquitin ligase, E6-AP, results in tissue-selective steroid hormone resistance and defects in reproduction. Mol Cell Biol. 2002;22:525–35.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Jones JO, An WF, Diamond MI. AR inhibitors identified by high-throughput microscopy detection of conformational change and subcellular localization. ACS Chem Biol. 2009;4:199–208.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Li H, Ban F, Dalal K, Leblanc E, Frewin K, Ma D, et al. Discovery of small-molecule inhibitors selectively targeting the DNA-binding domain of the human androgen receptor. J Med Chem. 2014;57:6458–67.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Zhou Y, Li W, Wang M, Zhang X, Zhang H, Tong X, et al. Competitive profiling of celastrol targets in human cervical cancer HeLa cells via quantitative chemical proteomics. Mol Biosyst. 2016;13:83–91.

    PubMed 
    Article 

    Google Scholar
     

  • Salminen A, Lehtonen M, Paimela T, Kaarniranta K. Celastrol: Molecular targets of Thunder God Vine. Biochemical Biophysical Res Commun. 2010;394:439–42.

    CAS 
    Article 

    Google Scholar
     

  • Lee JH, Koo TH, Yoon H, Jung HS, Jin HZ, Lee K, et al. Inhibition of NF-kappa B activation through targeting I kappa B kinase by celastrol, a quinone methide triterpenoid. Biochemical Pharmacol. 2006;72:1311–21.

    CAS 
    Article 

    Google Scholar
     

  • Seo HR, Seo WD, Pyun BJ, Lee BW, Jin YB, Park KH, et al. Radiosensitization by celastrol is mediated by modification of antioxidant thiol molecules. Chem-Biol Interact. 2011;193:34–42.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Hou Z, Huang S, Mei Z, Chen L, Guo J, Gao Y, et al. Inhibiting 3betaHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer. Cell Rep Med. 2022;3:100561.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Mei Z, Yang T, Liu Y, Gao Y, Hou Z, Zhuang Q, et al. Management of prostate cancer by targeting 3betaHSD1 after enzalutamide and abiraterone treatment. Cell Rep Med. 2022;3:100608.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Kregel S, Wang C, Han X, Xiao L, Fernandez-Salas E, Bawa P, et al. Androgen receptor degraders overcome common resistance mechanisms developed during prostate cancer treatment. Neoplasia 2020;22:111–9.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Proof-of-Concept with PROTACs in Prostate Cancer. Cancer Discov. 2020;10:1084. https://doi.org/10.1158/2159-8290.CD-NB2020-054.

  • Lim HY, Ong PS, Wang L, Goel A, Ding L, Li-Ann Wong A, et al. Celastrol in cancer therapy: Recent developments, challenges and prospects. Cancer Lett. 2021;521:252–67.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Shi J, Li J, Xu Z, Chen L, Luo R, Zhang C, et al. Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application. Front Pharmacol. 2020;11:558741.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Ramamoorthy S, Nawaz Z. E6-associated protein (E6-AP) is a dual function coactivator of steroid hormone receptors. Nucl Receptor Signal. 2008;6:e006.


    Google Scholar
     

  • Kishino T, Lalande M, Wagstaff J. UBE3A/E6-AP mutations cause Angelman syndrome. Nat Genet. 1997;15:70–3.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Matsuura T, Sutcliffe JS, Fang P, Galjaard RJ, Jiang YH, Benton CS, et al. De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet. 1997;15:74–7.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Gao X, Mohsin SK, Gatalica Z, Fu G, Sharma P, Nawaz Z. Decreased expression of e6-associated protein in breast and prostate carcinomas. Endocrinology 2005;146:1707–12.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Jiang YH, Armstrong D, Albrecht U, Atkins CM, Noebels JL, Eichele G, et al. Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. Neuron 1998;21:799–811.

    CAS 
    PubMed 
    Article 

    Google Scholar
     

  • Park JH, Walls JE, Galvez JJ, Kim M, Abate-Shen C, Shen MM, et al. Prostatic intraepithelial neoplasia in genetically engineered mice. Am J Pathol. 2002;161:727–35.

    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Shaffer PL, Jivan A, Dollins DE, Claessens F, Gewirth DT. Structural basis of androgen receptor binding to selective androgen response elements. Proc Natl Acad Sci. 2004;101:4758–63.

    CAS 
    PubMed 
    PubMed Central 
    Article 

    Google Scholar
     

  • Xu X, Li C, Gao X, Xia K, Guo H, Li Y, et al. Excessive UBE3A dosage impairs retinoic acid signaling and synaptic plasticity in autism spectrum disorders. Cell Res. 2018;28:48–68.

    CAS 
    PubMed 
    Article 

    Google Scholar