Unknown

Dataset Information

0

High-Risk Human Papillomavirus E7 Proteins Target PTPN14 for Degradation.


ABSTRACT: 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.High-risk human papillomaviruses (HPV) are the cause of cervical cancer, some other anogenital cancers, and a growing fraction of oropharyngeal carcinomas. The high-risk HPV E6 and E7 oncoproteins enable these viruses to cause cancer, and the mechanistic basis of their carcinogenic activity has been the subject of intense study. The high-risk E7 oncoprotein is especially important in the immortalization and transformation of human cells, which makes it a central component of HPV-associated cancer development. E7 oncoproteins interact with retinoblastoma family proteins, but for several decades, it has been recognized that high-risk HPV E7 oncoproteins have additional cancer-associated activities. We have determined that high-risk E7 proteins target the proteolysis of the cellular protein tyrosine phosphatase PTPN14 and find that this activity is correlated with the retinoblastoma-independent transforming activity of E7.

SUBMITTER: White EA 

PROVIDER: S-EPMC5030362 | BioStudies | 2016-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6668832 | BioStudies
2019-01-01 | S-EPMC6452706 | BioStudies
2017-01-01 | S-EPMC5355602 | BioStudies
1999-01-01 | S-EPMC83930 | BioStudies
2014-01-01 | S-EPMC3921905 | BioStudies
2019-01-01 | S-EPMC6685453 | BioStudies
2017-01-01 | S-EPMC5542257 | BioStudies
2020-01-01 | S-EPMC7087594 | BioStudies
2017-01-01 | S-EPMC5554117 | BioStudies
2020-01-01 | S-EPMC7338567 | BioStudies