Interaction of oncogenic papillomavirus E6 proteins with fibulin-1.
Human papillomavirus (HPV) infection is the primary risk factor for the development of cervical cancer. The papillomavirus E6 gene is essential for virus-induced cellular transformation and the viral life cycle. Important insight into the mechanism of E6 function came from the discovery that cancer-related HPV E6 proteins promote the degradation of the tumor suppressor p53. However, mounting evidence indicates that interaction with p53 does not mediate all E6 activities. To explore the p53-independent functions of E6, we performed a yeast two-hybrid screen and identified fibulin-1 as an E6 binding protein. Fibulin-1 is a calcium-binding plasma and extracellular matrix protein that has been implicated in cellular transformation and tumor invasion. The interaction between E6 and fibulin-1 was demonstrated by both in vitro and in vivo assays. Fibulin-1 is associated specifically with cancer-related HPV E6s and the transforming bovine papillomavirus type 1 E6. Significantly, overexpression of fibulin-1 specifically inhibited E6-mediated transformation. These results suggest that fibulin-1 plays an important role in the biological activities of E6.
Du
Minjie
M
Department of Medicine, University of Massachusetts Medical School, LRB Room 323, 364 Plantation Street, Worcester, MA 01605-2324, USA.
Fan
Xueli
X
Hong
Eva
E
Chen
Jason J
JJ
D016475:3T3 Cells; D020816:Amino Acid Motifs; D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D002478:Cells, Cultured; D005982:Glutathione Transferase / Q000378:metabolism; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D002135:Calcium-Binding Proteins; C118860:E6 protein, Human papillomavirus type 6; D009856:Oncogene Proteins, Viral; D016159:Tumor Suppressor Protein p53; C060820:fibulin; D005982:Glutathione Transferase