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Title: HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines

Abstract

Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.

Authors:
 [1];  [2];  [3];  [4];  [1]
  1. Department of Biology, Institute of Bioscience, Language and Exact Science, São Paulo State University, São Jose do Rio Preto (Brazil)
  2. Molecular Biology Laboratory, Centre for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo (ICESP), São Paulo (Brazil)
  3. Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo., São Paulo (Brazil)
  4. Department of Radiology and Oncology, Faculdade de Medicina, Universidade de São Paulo, São Paulo (Brazil)
Publication Date:
OSTI Identifier:
22581701
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 496; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARCINOGENESIS; CARCINOMAS; CELL PROLIFERATION; ONCOGENES; PROTEINS; RNA; SUBSTRATES; TUMOR CELLS

Citation Formats

Calmon, Marilia Freitas, Sichero, Laura, Boccardo, Enrique, Villa, Luisa Lina, and Rahal, Paula, E-mail: rahalp@yahoo.com.br. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines. United States: N. p., 2016. Web. doi:10.1016/J.VIROL.2016.05.016.
Calmon, Marilia Freitas, Sichero, Laura, Boccardo, Enrique, Villa, Luisa Lina, & Rahal, Paula, E-mail: rahalp@yahoo.com.br. HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines. United States. doi:10.1016/J.VIROL.2016.05.016.
Calmon, Marilia Freitas, Sichero, Laura, Boccardo, Enrique, Villa, Luisa Lina, and Rahal, Paula, E-mail: rahalp@yahoo.com.br. Thu . "HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines". United States. doi:10.1016/J.VIROL.2016.05.016.
@article{osti_22581701,
title = {HPV16 E6 regulates annexin 1 (ANXA1) protein expression in cervical carcinoma cell lines},
author = {Calmon, Marilia Freitas and Sichero, Laura and Boccardo, Enrique and Villa, Luisa Lina and Rahal, Paula, E-mail: rahalp@yahoo.com.br},
abstractNote = {Annexin 1 (ANXA1) is a substrate for E6AP mediated ubiquitylation. It has been hypothesized that HPV 16 E6 protein redirects E6AP away from ANXA1, increasing its stability and possibly contributing to viral pathogenesis. We analyzed ANXA1 expression in HPV-positive and negative cervical carcinoma-derived cells, in cells expressing HPV-16 oncogenes and in cells transduced with shRNA targeting E6AP. We observed that ANXA1 protein expression increased in HPV-16-positive tumor cells, in keratinocytes expressing HPV-16 E6wt (wild-type) or E6/E7 and C33 cells expressing HPV-16 E6wt. ANXA1 protein expression decreased in cells transfected with E6 Dicer-substrate RNAs (DsiRNA) and C33 cells cotransduced with HPV-16 E6wt and E6AP shRNA. Moreover, colony number and proliferation rate decreased in HPV16-positive cells transduced with ANXA1 shRNA. We observed that in cells infected with HPV16, the E6 binds to E6AP to degrade p53 and upregulate ANXA1. We suggest that ANXA1 may play a role in HPV-mediated carcinogenesis. - Highlights: • ANXA1 upregulation requires the presence of E6 and E6AP and is dependent on E6 integrity. • E6 binds to E6AP to degrade p53 and upregulate ANXA1 in cells infected with HPV16. • ANXA1 plays a role in cell proliferation in HPV-positive cervical cells.},
doi = {10.1016/J.VIROL.2016.05.016},
journal = {Virology},
number = ,
volume = 496,
place = {United States},
year = {Thu Sep 15 00:00:00 EDT 2016},
month = {Thu Sep 15 00:00:00 EDT 2016}
}