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.
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.
Chang
Hung-Shu
HS
Department of Life Sciences, College of Bioscience and Biotechnology, National Cheng Kung University, Taiwan, ROC. vhschang@gmail.com
Lin
Ching-Hui
CH
Yang
Chien-Hui
CH
Liang
Yuh-Jin
YJ
Yu
Winston C Y
WC
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D053938:DNA Fragmentation; D051765:Early Growth Response Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
D051765:Early Growth Response Transcription Factors; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D015513:Oncogene Proteins