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Regulation of Telomerase by Human Papillomaviruses

Year: 2005
Type: preprint
Abstract: The E6 oncoprotein of human papillomaviruses (HPVs) induces telomerase activity in primary human epithelial cells. This activity is dependent on association of E6 with E6AP, a cellular ubiquitin ligase. E6 activates the transcription of hTERT, the catalytic subunit of telomerase. E boxes near the start of hTERT transcription are required for E6; however, acetylated histones are only present in the E6 cells. We identified two isoforms of NFX1, a new binding partner of E6/E6AP. The NFX1- 91 isoform binds to an X-box motif located adjacent to the proximal E box, binds Sin3A and HDACs, repressing hTERT transcription. It preferentially binds E6/E6AP and is targeted for ubiquitin-mediated degradation. The NFX1-123 isoform has the opposite activity, increasing hTERT transcription or translation. This is the first example of viral oncoproteins disrupting regulation of telomerase, a critical event in tumorigenesis.
DOI: 10.1101/sqb.2005.70.041
Authors: D.A. GALLOWAY, L.C. GEWIN, H. MYERS, W. LUO, C. GRANDORI, R.A. KATZENELLENBOGEN, J.K. McDOUGALL
Institutions: Fred Hutch Cancer Center, Salk Institute for Biological Studies, University of California, San Francisco, University of California San Francisco Medical Center, Vanderbilt University, University of Washington
Language: English
Subfield: Physiology
Field: Medicine
Open Access status: bronze
Awards: Graduate and Postdoctoral Training in Viral Oncology, G281997290, G2852762695, G3229407453, HPV: Biology, Clinical Significance and Epidemiology, G7919879242, STD and AIDS Research Training Grant, Interactions of HPV Oncogenes With the p53 Pathway
OpenAlex ID: W2157014955
Cites: 43
Cited by: 25
Related to: 10