High-Risk Human Papillomavirus E7 Proteins Target PTPN14 for Degradation
MetadataShow full item record
CitationWhite, Elizabeth A., Karl Münger, and Peter M. Howley. 2016. “High-Risk Human Papillomavirus E7 Proteins Target PTPN14 for Degradation.” mBio 7 (5): e01530-16. doi:10.1128/mBio.01530-16. http://dx.doi.org/10.1128/mBio.01530-16.
AbstractABSTRACT The major transformation activity of the high-risk human papillomaviruses (HPV) is associated with the E7 oncoprotein. The interaction of HPV E7 with retinoblastoma family proteins is important for several E7 activities; however, this interaction does not fully account for the high-risk E7-specific cellular immortalization and transformation activities. We have determined that the cellular non-receptor protein tyrosine phosphatase PTPN14 interacts with HPV E7 from many genus alpha and beta HPV types. We find that high-risk genus alpha HPV E7, but not low-risk genus alpha or beta HPV E7, is necessary and sufficient to reduce the steady-state level of PTPN14 in cells. High-risk E7 proteins target PTPN14 for proteasome-mediated degradation, which requires the ubiquitin ligase UBR4, and PTPN14 is degraded by the proteasome in HPV-positive cervical cancer cell lines. Residues in the C terminus of E7 interact with the C-terminal phosphatase domain of PTPN14, and interference with the E7-PTPN14 interaction restores PTPN14 levels in cells. Finally, PTPN14 degradation correlates with the retinoblastoma-independent transforming activity of high-risk HPV E7.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29407742
- HMS Scholarly Articles