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Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600
Abstract
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 tumor 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.
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“p600 has been implicated in the regulation of anoikis signalling, and both high-risk and low-risk E7, as well as the E7 protein, from bovine papillomavirus 1 (BPV1), have been shown to associate with p600/UBR4 via residues in the CR1 amino-terminal domain [200,201]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [200]
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Metadata
- Authors
- Huh, K.-W., DeMasi, J., Ogawa, H., Nakatani, Y., Howley, P. M., & Münger, K.
- Affiliations
- The Channing Laboratory, Brigham and Women's Hospital and Department of Medicine, Department of Pathology, and Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2005-08
- Volume
- 102
- Issue
- 32
- Pages
- 11492-11497
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 176
- References
- 0
- Language
- en
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- Huh, K.-W., DeMasi, J., Ogawa, H., Nakatani, Y., Howley, P. M., & Münger, K. (2005). Association of the human papillomavirus type 16 E7 oncoprotein with the 600-kDa retinoblastoma protein-associated factor, p600. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0505337102
