Association of the Human Papillomavirus Type 16 E7 Oncoprotein with the 600-kDa Retinoblastoma Protein-Associated Factor, p600

The human papillomavirus type 16 (HPV-16) E7 gene encodes a multifunctional oncoprotein that can subvert multiple cellular regulatory pathways. The best-known cellular targets of the HPV-16 E7 oncoprotein are the retinoblastoma tumore suppressor protein pRB and the related pocket proteins p107 and p...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-08, Vol.102 (32), p.11492-11497
Main Authors: Huh, Kyung-Won, DeMasi, Joseph, Ogawa, Hidesato, Nakatani, Yoshihiro, Howley, Peter M., Münger, Karl
Format: Article
Language:English
Subjects:
3T3 cells
Adenovirus
Antibodies
Biological Sciences
Calmodulin-Binding Proteins - metabolism
Cell growth
Cell lines
Cell Proliferation
Cell Transformation, Viral - genetics
Cellular biology
Cervical cancer
HeLa Cells
Human papillomavirus
Human papillomavirus 16
Humans
Immunoprecipitation
Mass Spectrometry
Microscopy, Fluorescence
Multiprotein Complexes - isolation & purification
Multiprotein Complexes - metabolism
NIH 3T3 cells
Oncogene Proteins, Viral - metabolism
Papillomaviridae - metabolism
Papillomavirus E7 Proteins
Protein Binding
Proteins
RNA Interference
Transformed cell line
Viruses
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Summary:The human papillomavirus type 16 (HPV-16) E7 gene encodes a multifunctional oncoprotein that can subvert multiple cellular regulatory pathways. The best-known cellular targets of the HPV-16 E7 oncoprotein are the retinoblastoma tumore suppressor protein pRB and the related pocket proteins p107 and p130. However, there is ample evidence that E7 has additional cellular targets that contribute to its transforming potential. We isolated HPV-16 E7 associated cellular protein complexes by tandem affinity purification and mass spectrometry and identified the 600-kDa retinoblastoma protein associated factor, p600, as a cellular target of E7. Association of E7 with p600 is independent of the pocket proteins and is mediated through the N terminal E7 domain, which is related to conserved region 1 of the adenovirus E1A protein and importantly contributes to cellular transformation independent of pRB binding. Depletion of p600 protein levels by RNA interference substantially decreased anchorage-independent growth in HPV-positive and -negative human cancer cells. Therefore, p600 is a cellular target of E7 that regulates cellular pathways that contribute to anchorage-independent growth and cellular transformation.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0505337102