Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein

Tohru Kiyono, Atsuro Hiraiwa, Masatoshi Fujita, Yasuyuki Hayashi, Tetsu Akiyama, Masahide Ishibashi

Research output: Contribution to journalArticle

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Abstract

In the majority of cervical cancers, DNAs of high-risk mucosotpropic human papillomaviruses (HPVs), such as type 16, are maintained so as to express two vital proteins, E6 and E7, suggesting an essential importance to carcinogenesis. The high-risk HPV E6 proteins are known to inactivate p53 tumor suppressor protein but appear to have an additional, molecularly unknown function(s). In this study, we demonstrate that these E6 proteins can bind to the second PDZ domain of the human homologue of the Drosophila discs large tumor suppressor protein (hDLG) through their C-terminal XS/TXV/L (where X represents any amino acid, S/T serine or threonine, and V/L valine or leucine) motif. This finding is similar to the interaction between the adenomatous polyposis coil gene product and hDLG. E6 mutants losing the ability to bind to hDLG are no longer able to induce E6-dependent transformation of rodent cells. These results suggest an intriguing possibility that interaction between the E6 protein and hDLG or other PDZ domain-containing proteins could be an underlying mechanism in the development of HPV-associated cancers.

Original languageEnglish
Pages (from-to)11612-11616
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number21
DOIs
Publication statusPublished - Oct 14 1997
Externally publishedYes

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Tumor Suppressor Proteins
Oncogene Proteins
Drosophila
PDZ Domains
Proteins
Tumor Suppressor Protein p53
Aptitude
Valine
Human Development
Threonine
Leucine
Uterine Cervical Neoplasms
Serine
Rodentia
Carcinogenesis
Amino Acids
DNA
Genes
Neoplasms

All Science Journal Classification (ASJC) codes

  • General

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Binding of high-risk human papillomavirus E6 oncoproteins to the human homologue of the Drosophila discs large tumor suppressor protein. / Kiyono, Tohru; Hiraiwa, Atsuro; Fujita, Masatoshi; Hayashi, Yasuyuki; Akiyama, Tetsu; Ishibashi, Masahide.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 94, No. 21, 14.10.1997, p. 11612-11616.

Research output: Contribution to journalArticle

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AU - Ishibashi, Masahide

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