The viral death protein Apoptin interacts with Hippi, the protein interactor of Huntingtin-interacting protein 1.
Apoptin, a chicken anemia virus-encoded protein, induces apoptosis in human tumor cells but not in normal cells. The tumor-specific activity of Apoptin is correlated with its nuclear localization in tumor cells. In an attempt to elucidate the molecular mechanism of Apoptin-induced apoptosis, we identified human Hippi, the protein interactor and apoptosis co-mediator of Huntingtin interacting protein 1, as one of the Apoptin-associated proteins by yeast two-hybrid screen. We also demonstrated that Hippi could interact with Apoptin both in vitro and in human cells. Furthermore, subcellular localization studies showed that Hippi and Apoptin perfectly colocalized in the cytoplasm of normal human HEL cells, whereas in cancerous HeLa cells most Apoptin and Hippi were located separately in the nucleus and cytoplasm and, thus, showed only a modest colocalization. Mapping studies indicate that Hippi binds within the self-multimerization domain of Apoptin, and Apoptin binds to the C-terminal half of Hippi, including its death effector domain-like motif. Our results suggest that the Apoptin-Hippi interaction may play a role in the suppression of apoptosis in normal cells.
Cheng
Chih-Mei
CM
Department of Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
Huang
Shiao-ping
SP
Chang
Yung-Fu
YF
Chung
Wen-Yuan
WY
Yuo
Chung-Yee
CY
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry / Q000378:metabolism*; D036022:Capsid Proteins; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins; D006367:HeLa Cells; D006801:Humans; D017434:Protein Structure, Tertiary; D020798:Two-Hybrid System Techniques
D048868:Adaptor Proteins, Signal Transducing; D036022:Capsid Proteins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C073368:HIP1 protein, human; C489536:Hip1 protein, mouse; C499179:IFT57 protein, human; C091717:VP3 protein, Chicken anemia virus