title: Human RAD23 homolog A is required for the nuclear translocation of apoptosis-inducing factor during induction of cell death.
abstract: BACKGROUND
  During the initiation of cell death, mitochondrial protein, apoptosis-inducing factor (AIF), is transported to the nucleus. The mechanism of AIF nuclear translocation, however, is not clear. After protein synthesis, the AIF is originally targetted to the mitochondria, and the nuclear targetting is a secondary event. Therefore, we hypothesised that the nuclear translocation of AIF could be achieved by a novel pathway.
  
  
  RESULTS
  By using yeast two-hybrid assay, we identified the human UV excision repair protein RAD23 homolog A (hHR23A) interacts with AIF and their interaction was confirmed by co-immunoprecipitation and fluorescence resonance energy transfer microscopy. Silencing the RAD23A gene expression inhibits the nuclear transportation of AIF and increases cisplatin resistance. Silencing the karyopherin alpha 2 (KPNA2) gene expression, however, did not affect the nuclear import of AIF. Moreover, 2,4-dinitrophenol inhibits staurosporine-induced nuclear translocation of AIF and increases cisplatin resistance.
  
  
  CONCLUSIONS
  These results suggest that hHR23A is required for the nuclear translocation of AIF during induction of cell death, and this process is energy dependent, but independent of karyopherins.
authors: Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, Republic of China.
authors: Janaki N
authors: JN
authors: Sudhakar
authors: Kuan-Chih
authors: KC
authors: Chow
mesh_terms: D021581:Active Transport, Cell Nucleus; D051033:Apoptosis Inducing Factor / Q000378:metabolism*; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
chemical_list: D051033:Apoptosis Inducing Factor; D004268:DNA-Binding Proteins; C086985:RAD23A protein, human; D045643:DNA Repair Enzymes
keywords: Apoptosis-inducing factor; Cisplatin resistance; FRET; Nuclear translocation; hHR23A