Dataset Information

Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding.

ABSTRACT: The E7 oncoprotein of bovine papillomavirus type 1 (BPV-1) is required for the full transformation activity of the virus. However, the mechanism by which E7 contributes to cellular transformation is unknown. To address this question, we used the proteomic approach of tandem affinity purification to identify cellular proteins that are in complex with E7, and identified the 600-kDa protein, p600, as a binding partner of E7. The ability of E7 to complex with p600 correlated with its ability to enhance anchorage independence of BPV-1 E6-expressing cells. Furthermore, E7 mutant proteins impaired in their ability to bind p600 were transformation defective. Additionally, knockdown of p600 reduced transformation of cells expressing both BPV-1 E6 and E7, as well as E6 alone, suggesting that the ability of E7 to transformed cells is mediated, at least in part, through its ability to bind p600. These data complement work that shows that HPV16 E7 also interacts with p600, and that this interaction correlates with the ability of HPV16 E7 to transform cells. These studies thus identify p600 as a shared target of the E7 proteins of multiple papillomaviruses.

SUBMITTER: DeMasi J

PROVIDER: S-EPMC1182553 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Human papillomavirus (HPV) has been identified as the primary etiologic factor of cervical cancer, the fourth leading cause of cancer death in females worldwide. We have previously shown that coadministration of DNA encoding L1 capsid protein of Bovine papillomavirus (BPV) can enhance the antigen-specific immune response elicited by a therapeutic HPV16-E7 DNA vaccination. In this study, we sought to generate and evaluate the immunogenicity of a therapeutic HPV16-E7 DNA vaccine that encodes the fusion construct of HPV16-E7 and BPV-L1.We generated a therapeutic HPV16-E7 DNA vaccine construct, pcDNA3-BPVL1-E7(49-57), encoding the fusion sequence of full-length BPVL1 protein and a murine E7 antigenic epitope, aa49-57. Transfecting 293-Db cells with pcDNA3-BPVL1-E7(49-57) demonstrated that this DNA construct can effectively lead to the presentation of E7 epitope for the activation of E7-specific CD8+ T cells in vitro. Intramuscular vaccination of pcDNA3-BPVL1-E7(49-57) with electroporation generated a stronger E7-specific CD8+ T cell-mediated immune response than coadministration of pcDNA3-BPVL1 and pcDNA3-E7(49-57) in C57BL/6 mice. Furthermore, we observed that the strong E7-specific CD8+ T cell response elicited by pcDNA3-BPVL1-E7(49-57) vaccination translated into potent protective and therapeutic antitumor effects in C57BL/6 mice against HPV16-E7 expressing TC-1 tumor cells. Finally, using antibody depletion experiment, we showed that the antitumor immune response generated by pcDNA3-BPVL1-E7(49-57) is CD8+ T cell dependent, and CD4+ T cell and NK cell independent.Treatment with fusion construct of BPV-L1 and HPV16-E7 epitope can elicit effective E7-specific antitumor immune response in mice. Due to the potential ability of the fusion DNA construct to also trigger immune responses specific to the L1 protein, the current study serves to support future design of HPV DNA vaccines encoding fusion HPVL1-E6/E7 constructs for the generation of both T cell and B cell mediated immune responses against HPV infections and associated diseases.

Dataset Information

Bovine papillomavirus E7 transformation function correlates with cellular p600 protein binding.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure