Regulation of DNA topoisomerase IIalpha stability by the ECV ubiquitin ligase complex.
In this study, we attempted to elucidate the E3 ubiquitin ligase for topo IIalpha. When cullins and VHL were ectopically expressed in HT1080 and HEK293T cells, topo IIalpha was degraded most prominently in cullin 2- and VHL-expressing cells. Cullin 2 and the beta domain (aa 114-123) of VHL, a subunit ... of the ECV (Elongin B/C-cullin 2-VHL protein) complex, specifically interact with the ATPase domain of topo IIalpha. We identified that topo IIalpha associated with endogenous Elongin C. In HT1080 cells co-transfected with deletion mutants of topo IIalpha GRDD (glucose-regulated destruction domain) and VHL, topo IIalpha was degraded by VHL expression. These results demonstrate that ECV acts as E3 ubiquitin ligase targeting GRDD-independent topo IIalpha to the ubiquitin-proteasome pathway.
Mesh Terms:
Adenosine Triphosphatases, Antigens, Neoplasm, Cell Line, Cullin Proteins, DNA Topoisomerases, Type II, DNA-Binding Proteins, Enzyme Stability, Humans, Protein Structure, Tertiary, Transcription Factors, Ubiquitin-Protein Ligases, Von Hippel-Lindau Tumor Suppressor Protein
Adenosine Triphosphatases, Antigens, Neoplasm, Cell Line, Cullin Proteins, DNA Topoisomerases, Type II, DNA-Binding Proteins, Enzyme Stability, Humans, Protein Structure, Tertiary, Transcription Factors, Ubiquitin-Protein Ligases, Von Hippel-Lindau Tumor Suppressor Protein
Biochem. Biophys. Res. Commun.
Date: Nov. 06, 2009
PubMed ID: 19695223
View in: Pubmed Google Scholar
Download Curated Data For This Publication
139989
Switch View:
- Interactions 3