Alteration of Rb binding to HPV 18 E7 modified by transglutaminase 2 with different type of polyamines.
High-risk human papillomavirus (HPV) E7 is a major oncoprotein that plays a crucial role in the development of cervical cancer. A previous study showed that transglutaminase (TGase) 2 catalyzes the incorporation of polyamines into HPV 18 E7 protein, and thereby diminishes its ability to bind Rb. Therefore, TGase 2 activity may be implicated in a suppressive function of host against HPV-induced carcinogenesis. To better understand the nature of polyamination of HPV 18 E7, we investigated the Rb binding of E7 polyaminated in vitro with different type of polyamines. The incorporation of spermine diminished the Rb binding of E7 more profoundly compared with that of spermidine, suggesting that either the additional positive charge or a steric effect or both may have altered the chemical or structural properties of the protein. In addition, the treatment of either spermidine or spermine in cultured cell system reduced the ability of E7 to inactivate Rb with a TGase activity-dependent manner. Spermine was more effective in inhibiting E7 activity than spermidine. These results may provide the basis for future investigation aiming at delineating the significance of polyamine metabolism on HPV E7 functions.
Jeon
Ju-Hong
JH
Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Seoul National University College of Medicine, 28 Yongon Dong, Seoul 110-799, Korea.
Cho
Sung-Yup
SY
Kim
Chai-Wan
CW
Shin
Dong-Myung
DM
Jang
Gi-Yong
GY
Lee
Hye-Jin
HJ
Kang
Heun-Soo
HS
Park
Sang-Chul
SC
Kim
In-Gyu
IG
D000588:Amines / Q000737:chemistry; D019921:Biotinylation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D050684:E2F Transcription Factors / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005809:Genes, Regulator; D016161:Genes, Retinoblastoma; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008956:Models, Chemical; D009856:Oncogene Proteins, Viral / Q000378:metabolism / Q000502:physiology*; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011994:Recombinant Proteins / Q000737:chemistry; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013095:Spermidine / Q000737:chemistry; D013096:Spermine / Q000737:chemistry; D015533:Transcriptional Activation; D014162:Transfection; D011503:Transglutaminases / Q000378:metabolism*
D000588:Amines; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; C052633:E7 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; D011073:Polyamines; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D013096:Spermine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D005982:Glutathione Transferase; D019204:GTP-Binding Proteins; D013095:Spermidine