Transglutaminase 2 inhibits Rb binding of human papillomavirus E7 by incorporating polyamine

Ju Hong Jeon, Kyung Ho Choi, Sung Yup Cho, Chai Wan Kim, Dong Myung Shin, Joon Cheol Kwon, Kye Yong Song, Sang Chul Park, In Gyu Kim

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Transglutaminase 2 (TGase 2) is one of a family of enzymes that catalyze protein modification through the incorporation of polyamines into substrates or the formation of protein crosslinks. However, the physiological roles of TGase 2 are largely unknown. To elucidate the functions of TGase 2, we have searched for its interacting proteins. Here we show that TGase 2 interacts with E7 oncoprotein of human papillomavirus type 18 (HPV18) in vitro and in vivo. TGase 2 incorporates polyamines into a conserved glutamine residue in the zinc-binding domain of HPV18 E7 protein. This modification mediates the inhibition of E7's Rb binding ability. In contrast, TGase 2 does not affect HPV16 E7, due to absence of a glutamine residue at this polyamination site. Using E7 mutants, we demonstrate that TGase 2-dependent inhibition of HPV E7 function correlates with the presence of the polyamination site. Our results indicate that TGase 2 is an important cellular interfering factor and define a novel host-virus interaction, suggesting that the inability of TGase 2 to inactivate HPV16 E7 could explain the high prevalence of HPV16 in cervical cancer.

Original languageEnglish (US)
Pages (from-to)5273-5282
Number of pages10
JournalEMBO Journal
Volume22
Issue number19
DOIs
StatePublished - Oct 1 2003

Keywords

  • Host-virus interaction
  • Human papillomavirus E7 oncoprotein
  • Polyamination
  • Transglutaminase 2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Jeon, J. H., Choi, K. H., Cho, S. Y., Kim, C. W., Shin, D. M., Kwon, J. C., Song, K. Y., Park, S. C., & Kim, I. G. (2003). Transglutaminase 2 inhibits Rb binding of human papillomavirus E7 by incorporating polyamine. EMBO Journal, 22(19), 5273-5282. https://doi.org/10.1093/emboj/cdg495