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Viruses 2017, 9(7), 175; doi:10.3390/v9070175

SOX2 as a New Regulator of HPV16 Transcription

1
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología (INCan)/Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 14080, Mexico
2
Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ)/Unidad Periférica del Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 14080, Mexico
3
Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Ciudad de México 04510, Mexico
*
Author to whom correspondence should be addressed.
Academic Editor: Joanna Parish
Received: 15 May 2017 / Revised: 15 May 2017 / Accepted: 27 June 2017 / Published: 5 July 2017
(This article belongs to the Section Animal Viruses)
View Full-Text   |   Download PDF [2343 KB, uploaded 5 July 2017]   |  

Abstract

Persistent infections with high-risk human papillomavirus (HPV) constitute the main risk factor for cervical cancer development. HPV16 is the most frequent type associated to squamous cell carcinomas (SCC), followed by HPV18. The long control region (LCR) in the HPV genome contains the replication origin and sequences recognized by cellular transcription factors (TFs) controlling viral transcription. Altered expression of E6 and E7 viral oncogenes, modulated by the LCR, causes modifications in cellular pathways such as proliferation, leading to malignant transformation. The aim of this study was to identify specific TFs that could contribute to the modulation of high-risk HPV transcriptional activity, related to the cellular histological origin. We identified sex determining region Y (SRY)-box 2 (SOX2) response elements present in HPV16-LCR. SOX2 binding to the LCR was demonstrated by in vivo and in vitro assays. The overexpression of this TF repressed HPV16-LCR transcriptional activity, as shown through reporter plasmid assays and by the down-regulation of endogenous HPV oncogenes. Site-directed mutagenesis revealed that three putative SOX2 binding sites are involved in the repression of the LCR activity. We propose that SOX2 acts as a transcriptional repressor of HPV16-LCR, decreasing the expression of E6 and E7 oncogenes in a SCC context. View Full-Text
Keywords: human papillomavirus; HPV; LCR; SOX2; transcriptional regulation human papillomavirus; HPV; LCR; SOX2; transcriptional regulation
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Martínez-Ramírez, I.; del-Castillo-Falconi, V.; Mitre-Aguilar, I.B.; Amador-Molina, A.; Carrillo-García, A.; Langley, E.; Zentella-Dehesa, A.; Soto-Reyes, E.; García-Carrancá, A.; Herrera, L.A.; Lizano, M. SOX2 as a New Regulator of HPV16 Transcription. Viruses 2017, 9, 175.

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