DDB2 is a novel AR interacting protein and mediates AR ubiquitination/ degradation
Journal
International Journal of Biochemistry and Cell Biology
Journal Volume
44
Journal Issue
11
Pages
1952-1961
Date Issued
2012
Author(s)
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. ? 2012 Elsevier Ltd.
Subjects
AR; CUL4A-DDB1; DDB2; DNA damage; Prostate cancer
SDGs
Other Subjects
androgen; androgen receptor; cullin; damaged DNA binding protein 2; DNA binding protein; protein p53; RNA; unclassified drug; article; cell growth; DNA damage; gene expression; human; human cell; prostate cancer; protein degradation; protein expression; protein stability; transcription regulation; ubiquitination; Cell Line; Cell Proliferation; Cullin Proteins; DNA Damage; DNA-Binding Proteins; Humans; Male; Prostatic Neoplasms; Protein Binding; Protein Interaction Mapping; Protein Stability; Protein Structure, Tertiary; Proteolysis; Receptors, Androgen; Tumor Suppressor Protein p53; Ubiquitination
Type
journal article