Human papillomavirus oncoprotein E6 binds to the C-terminal region of human minichromosome maintenance 7 protein.
Oncoprotein E6 of the human papillomavirus (HPV) associated with cervical cancer (HPV-16 and -18) degrades tumor suppressor protein p53, but seems to have p53-independent transforming functions. We searched for other cellular targets for the N-terminal region of HPV-16 E6 using a yeast two-hybrid system. The E6 was found to bind to the C-terminal region of a human minichromosome maintenance 7 (hMCM7) protein, which is a component of replication licensing factors. The full-length hMCM7 translated in vitro was capable of binding to bacterially expressed E6. In yeast cells the E6s of the cancer-associated HPVs (HPV-16, -18, and -58) bound to hMCM7 more strongly than those of the HPVs associated with a benign tumor (HPV-6 and -11). Binding of E6 with hMCM7 may cause chromosomal abnormalities found in the human cells expressing E6s of oncogenic HPVs.
Division of Molecular Genetics, National Institute of Infectious Diseases, Tokyo, Japan. ikuki@nih.go.jp
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Kukimoto
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Aihara
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Yoshiike
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Kanda
D001665:Binding Sites; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C068651:E6 protein, Human papillomavirus type 16; C052603:E6 protein, Human papillomavirus type 18; D009687:Nuclear Proteins; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7