The human papillomavirus-16 (HPV-16) oncoprotein E7 conjugates with and mediates the role of the transforming growth factor-beta inducible early gene 1 (TIEG1) in apoptosis |
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| Authors: | Hung-Shu Chang Ching-Hui Lin Chien-Hui Yang Yuh-Jin Liang Winston C.Y. Yu |
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| Affiliation: | 1. Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Taiwan, ROC;2. National Institute of Cancer Research, National Health Research Institutes, Miaoli County, Taiwan, ROC;1. Laboratory of Cell Biology, Institute for Medical Sciences, Ajou University, Suwon, Republic of Korea;2. Department of Dermatology, Ajou University, Suwon, Republic of Korea;3. Brain Korea 21 Project for Medical Science, Republic of Korea;1. Department of Hematology, Qilu Hospital, Shandong University, Jinan, China;2. Center for Reproductive Medicine, Shandong University, Jinan, China;3. Medical School of Shandong University, Jinan, China;4. Department of Blood Cell Components Separation, Blood Center of Shandong Province, Jinan, China;5. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, China;1. Department of Clinical Medicine, Shanghai Tenth People''s Hospital Tongji University School of Medicine, Shanghai 200072, China;2. Department of Central Laboratory, Shanghai Tenth People''s Hospital of Tongji University, Tongji University School of Medicine, Shanghai 200072, China;3. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai, 200241, China;4. Shanghai Tenth People''s Hospital of Tongji University, Tongji University School of Medicine, Shanghai 200072, China;5. School of Life Science and Technology, Tongji University, Shanghai 200072, China;6. Shanghai Jiao Tong University Affiliated Sixth People''s Hospital, Shanghai, 201306, China;1. Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea;2. Department of Laboratory Animal Resources, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul 122-704, Republic of Korea;3. Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Republic of Korea;4. Genomic Informatics Center, Han Kyung National University, Anseong 456-749, Republic of Korea;5. Laboratory of Developmental Genetics, School of Medicine, Inha University, Incheon 400-712, Republic of Korea;6. Department of Biomaterials Science, College of Natural Resources & Life Science, Pusan National University/PNU-Laboratory Animal Resources Center, Miryang 627-706, Republic of Korea |
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| Abstract: | The human papillomavirus (HPV) oncoprotein E7 is a major transforming protein. The E7 protein does not possess intrinsic enzymatic activity, but rather functions through direct and indirect interactions with cellular proteins, several of which are well known cellular tumor suppressors. Using the yeast two-hybrid system, we found that transforming growth factor-beta inducible early gene 1 (TIEG1), a member of the Krüppel-like family (KLF) that has been implicated as a putative tumor suppressor, interacts and forms a specific complex with HPV-16 E7. TIEG1 has been shown to mimic the effects of TGF-beta in various carcinoma cells and plays a critical role in the apoptotic cascade. Our results indicate that E7 binds to the C-terminus of TIEG1 and induces its degradation via the ubiquitin pathway. E7 not only increased the ubiquitination of TIEG1 but also influenced the ability of TIEG1 to affect apoptosis. Our results suggest that suppression of TIEG1-mediated signaling by E7 may contribute to HPV-associated carcinogenesis. |
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