HPV E6 and E7 oncoproteins cooperatively alter the expression of Disc Large 1 polarity protein in epithelial cells

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dc.citation.titleBMC Cancer
dc.citation.volume20
dc.creatorDizanzo, María Paula
dc.creatorMarziali, Federico Emanuel
dc.creatorBrunet Avalos, Clarise
dc.creatorBugnon Valdano, Marina Paula
dc.creatorLeiva, Santiago Gabriel
dc.creatorCavatorta, Ana Laura
dc.creatorGardiol, Daniela
dc.date.accessioned2024-05-31T16:20:27Z
dc.date.available2024-05-31T16:20:27Z
dc.date.issued2020-04-07
dc.description.abstractBackground: Persistent infection with high-risk Human Papillomavirus (HPVs) is associated with the development of cervical cancer. The transforming capacity of these viruses relies on the cooperative action of the E6 and E7 viral oncoproteins. Among the oncogenic activities of E6, the interaction and interference with cell polarity PDZ proteins have been well established. One of the most characterized PDZ targets of HPV E6 is human Disc large 1 (DLG1), a scaffolding protein involved in the control of cell polarity and proliferation. Interestingly, in cervical squamous intraepithelial lesions, alterations in DLG1 expression were observed in association to tumour progression. Moreover, the expression of both HPV E6 and E7 proteins may be responsible for the changes in DLG1 abundance and cell localization observed in the HPV-associated lesions. Methods: Due to the relevance of DLG1 deregulation in tumour development, we have performed an in-depth investigation of the expression of DLG1 in the presence of the HPV oncoproteins in epithelial cultured cells. The effects of HPV E6 and E7 proteins on DLG1 abundance and subcellular localization were assessed by western blot and confocal fluorescence microscopy, respectively. Results: We demonstrated that the relative abundance of HPV-18 E6 and DLG1 is a key factor that contributes to defining the expression abundance of both proteins. We also show here that a high expression level of DLG1 may negatively affect HPV-18 E6 nuclear expression. Moreover, the co-expression of HPV-18 E6 and E7 produces a striking effect on DLG1 subcellular localization and a co-distribution in the cytoplasmic region. Interestingly, HPV-18 E7 is also able to increase DLG1 levels, likely by rescuing it from the E6-mediated proteasomal degradation. Conclusions: In general, the data suggest that HPV-18 E6 and E7 may have opposing activities in regards to the regulation of DLG1 levels and may cooperatively contribute to its subcellular redistribution in the HPV context. These findings constitute a step forward in understanding the differential expression of DLG1 during tumour progression in an HPV-associated model.
dc.description.filFil: Dizanzo, María Paula. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Marziali, Federico Emanuel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Brunet Avalos, Clarise. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Bugnon Valdano, Marina Paula. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Leiva, Santiago Gabriel. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Cavatorta, Ana Laura. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.filFil: Gardiol, Daniela. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología Molecular y Celular de Rosario (CONICET-IBR); Argentina.
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET)
dc.description.sponsorshipMinisterio de Salud de la República Argentina. Instituto Nacional del Cáncer
dc.format.extent1-13
dc.identifier.issn1471-2407
dc.identifier.urihttps://hdl.handle.net/2133/27118
dc.language.isoen
dc.publisherBMC
dc.relation.publisherversionhttps://bmccancer.biomedcentral.com/articles/10.1186/s12885-020-06778-5#Ack1
dc.relation.publisherversionhttps://doi.org/10.1186/s12885-020-06778
dc.rightsopenAccess
dc.rights.holderDizanzo, María Paula
dc.rights.holderMarziali, Federico Emanuel
dc.rights.holderBrunet Avalos, Clarise
dc.rights.holderBugnon Valdano, Marina Paula
dc.rights.holderLeiva, Santiago Gabriel
dc.rights.holderCavatorta, Ana Laura
dc.rights.holderGardiol, Daniela
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectDLG1
dc.subjectHPV
dc.subjectHPV oncoprotein
dc.subjectExpression
dc.subjectCancer
dc.titleHPV E6 and E7 oncoproteins cooperatively alter the expression of Disc Large 1 polarity protein in epithelial cells
dc.typearticulo
dc.type.versionpublishedVersion

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