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Int J Biochem Cell Biol ; 44(11): 1952-61, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22846800

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.


Subject(s)
DNA-Binding Proteins/metabolism , Proteolysis , Receptors, Androgen/metabolism , Ubiquitination , Cell Line , Cell Proliferation , Cullin Proteins/metabolism , DNA Damage , DNA-Binding Proteins/chemistry , Humans , Male , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , Protein Binding , Protein Interaction Mapping , Protein Stability , Protein Structure, Tertiary , Receptors, Androgen/genetics , Tumor Suppressor Protein p53/metabolism
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