title: Implications of ubiquitin ligases in castration-resistant prostate cancer.
abstract: OBJECTIVE
  Significant advances have been made in the study of ubiquitination-mediated regulation of androgen receptor (AR). This review will highlight the latest developments in the mechanisms by which E3 ubiquitin ligases control AR activity, with implications in castration-resistant prostate cancer (CRPC).
  
  
  RESULTS
  Several ubiquitin ligases have been identified to interact with and ubiquitinate AR, and consequently regulate the AR transcriptional programme. Different ubiquitin ligases can use distinct mechanisms to modulate the expression of AR target genes, including local turnover of AR chromatin complex, recruitment of AR coactivators and global AR stability. The expression or activity of ubiquitin ligases can be altered in prostate cancer and thus contribute to the growth of androgen-insensitive prostate cancer cells by modulating the AR transcriptional activity.
  
  
  CONCLUSIONS
  Understanding the regulation of AR transcriptional activity by ubiquitin ligases will contribute to the elucidation of mechanisms underlying AR reactivation that is believed to drive the development of CRPC. Ubiquitin ligases could potentially serve as promising targets for developing therapeutics in the treatment of advanced prostate cancers.
authors: aDepartment of Biochemistry and Molecular Biology bGreenebaum Cancer Center, University of Maryland School of Medicine cBaltimore VA Medical Center, Baltimore, Maryland, USA.
authors: Jianfei
authors: J
authors: Qi
authors: Lingling
authors: L
authors: Fan
authors: Arif
authors: A
authors: Hussain
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects* / Q000502:physiology
chemical_list: D011944:Receptors, Androgen; D044767:Ubiquitin-Protein Ligases