Article
- The EMBO Journal (2003) 22, 5273 - 5282
- doi:10.1093/emboj/cdg495
Subject Categories:
Transglutaminase 2 inhibits Rb binding of human papillomavirus E7 by incorporating polyamine
Ju-Hong Jeon1, Kyung-Ho Choi1, Sung-Yup Cho1, Chai-Wan Kim1, Dong-Myung Shin1, Joon-Cheol Kwon1, Kye-Yong Song2, Sang-Chul Park1 and In-Gyu Kim1
- Department of Biochemistry and Molecular Biology/Aging and Apoptosis Research Center (AARC), Seoul National University College of Medicine, 28 Yongon Dong, Seoul 110-799, Korea
- Department of Pathology, Chung-Ang University College of Medicine, Seoul 156-756, Korea
Correspondence to:
In-Gyu Kim, E-mail: igkim@plaza.snu.ac.kr
Received 2 February 2003; Accepted 8 August 2003; Revised 7 August 2003
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.
Keywords:
- host–virus interaction,
- human papillomavirus E7 oncoprotein,
- polyamination,
- transglutaminase 2
