title: DDB2 is a novel AR interacting protein and mediates AR ubiquitination/degradation.
abstract: Damaged DNA-binding protein 2 (DDB2), a protein that binds damaged DNA, is a DDB1 and CUL4-associated factor. This study is the first to demonstrate that DDB2 is a novel androgen receptor (AR)-interacting protein; and mediating contact with AR and CUL4A-DDB1 complex for AR ubiquitination/degradation. DNA damage induces both p53 and DDB2 gene expression those two can inhibit AR expression. The former reduces AR via transcription regulation but the latter via proteosome degradation. Thereby DDB2 can inhibit cell growth rate in AR-expressing cells (LNCaP) but not in AR-null cells (PC3). Hence DDB2 may be a potential regimen for prostate cancer treatment, especially in androgen-refractory patients harboring high amount of AR who cannot be cured by androgen ablation.
authors: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors: Szu-Wei
authors: SW
authors: Chang
authors: Chieh-Hao
authors: CH
authors: Su
authors: Hsuan-Hao
authors: HH
authors: Chen
authors: Chu-Wei
authors: CW
authors: Huang
authors: Li-Pen
authors: LP
authors: Tsao
authors: Yeou-Ping
authors: YP
authors: Tsao
authors: Show-Li
authors: SL
authors: Chen
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D044842:Cullin Proteins / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D025941:Protein Interaction Mapping; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C410798:AR protein, human; C114234:CUL4A protein, human; D044842:Cullin Proteins; C091435:DDB1 protein, human; C117669:DDB2 protein, human; D004268:DNA-Binding Proteins; D011944:Receptors, Androgen; D016159:Tumor Suppressor Protein p53