Beta-Genus Human Papillomavirus 8 E6 Destabilizes the Host Genome by Promoting p300 Degradation

Dacus, Dalton; Wallace, Nicholas A.

doi:10.3390/v13081662

Cited by 12 publications

(6 citation statements)

References 136 publications

(191 reference statements)

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“…Resulting hyperproliferative epithelium can form papillomas and represents a resource of new virus progeny. 21 In conjunction with chronic UV-exposure, however, cutaneous PVs interfere with DNA repair, 54,55 favoring the accumulation of driver mutations, for example, in the p53 gene, 14 that apparently results in both favoring the outgrowth of cells with a pathophysiological network counterselective for viral replication and making viral gene expression dispensable (Figures 2A and 3B).…”

Section: Discussionmentioning

confidence: 99%

Spatial tissue proteomics reveals distinct landscapes of heterogeneity in cutaneous papillomavirus‐induced keratinocyte carcinomas

Schäfer

Schneider

Müller

et al. 2023

Journal of Medical Virology

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Infection with certain cutaneous human papillomaviruses (HPV), in conjunction with chronic ultraviolet (UV) exposure, are the major cofactors of non‐melanoma skin cancer (NMSC), the most frequent cancer type worldwide. Cutaneous squamous cell carcinomas (SCCs) as well as tumors in general represent three‐dimensional entities determined by both temporal and spatial constraints. Whole tissue proteomics is a straightforward approach to understand tumorigenesis in better detail, but studies focusing on different progression states toward a dedifferentiated SCC phenotype on a spatial level are rare. Here, we applied an innovative proteomic workflow on formalin‐fixed, paraffin‐embedded (FFPE) epithelial tumors derived from the preclinical animal model Mastomys coucha. This rodent is naturally infected with its genuine cutaneous papillomavirus and closely mimics skin carcinogenesis in the context of cutaneous HPV infections in humans. We deciphered cellular networks by comparing diverse epithelial tissues with respect to their differentiation level and infection status. Our study reveals novel regulatory proteins and pathways associated with virus‐induced tumor initiation and progression of SCCs. This approach provides the basis to better comprehend the multistep process of skin carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Spatial tissue proteomics reveals distinct landscapes of heterogeneity in cutaneous papillomavirus‐induced keratinocyte carcinomas

Schäfer

Schneider

Müller

et al. 2023

Journal of Medical Virology

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“…The interference with UV damage repair by HPV5 and HPV8 E6 causes a more frequent collapse of replication forks into mutagenic DSBs. Erroneous DSB repair can cause the loss of large regions of DNA, chromosome translocation/rearrangements, and aneuploidy [ 67 , 68 ]. Two major pathways, homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to repair DSBs with high fidelity.…”

Section: Beta Hpv and Genomic Instabilitymentioning

confidence: 99%

Beta HPV Deregulates Double-Strand Break Repair

Wallace

2022

Viruses

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Beta human papillomavirus (beta HPV) infections are common in adults. Certain types of beta HPVs are associated with nonmelanoma skin cancer (NMSC) in immunocompromised individuals. However, whether beta HPV infections promote NMSC in the immunocompetent population is unclear. They have been hypothesized to increase genomic instability stemming from ultraviolet light exposure by disrupting DNA damage responses. Implicit in this hypothesis is that the virus encodes one or more proteins that impair DNA repair signaling. Fluorescence-based reporters, next-generation sequencing, and animal models have been used to test this primarily in cells expressing beta HPV E6/E7. Of the two, beta HPV E6 appears to have the greatest ability to increase UV mutagenesis, by attenuating two major double-strand break (DSB) repair pathways, homologous recombination, and non-homologous end-joining. Here, we review this dysregulation of DSB repair and emerging approaches that can be used to further these efforts.

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“…Inhibition of TGF-β and NOTCH signaling by E6 inhibits differentiation of squamous epithelial cells [ 98 , 99 , 101 , 105 ]. Additionally, the cutaneous HPV E6 proteins also thwart the DNA damage response and increase the susceptibility of the infected cells to UV-induced DNA damage at least in part through interactions with the p300 protein [ 106 , 107 , 108 , 109 ]. While cutaneous HPV E6 proteins do not detectably interact with E6AP and thus do not target p53 for degradation, a study that investigated the effects of β-HPV E6 proteins on p53 reported that a subset of cutaneous HPV E6 proteins may inhibit activation of p53 by DNA damage [ 110 ].…”

Section: Biological Activities Of E6 and E7 Proteins Encoded By Cutan...mentioning

confidence: 99%

Molecular Mechanisms of MmuPV1 E6 and E7 and Implications for Human Disease

Romero-Masters

Lambert

Münger

2022

Viruses

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Human papillomaviruses (HPVs) cause a substantial amount of human disease from benign disease such as warts to malignant cancers including cervical carcinoma, head and neck cancer, and non-melanoma skin cancer. Our ability to model HPV-induced malignant disease has been impeded by species specific barriers and pre-clinical animal models have been challenging to develop. The recent discovery of a murine papillomavirus, MmuPV1, that infects laboratory mice and causes the same range of malignancies caused by HPVs provides the papillomavirus field the opportunity to test mechanistic hypotheses in a genetically manipulatable laboratory animal species in the context of natural infections. The E6 and E7 proteins encoded by high-risk HPVs, which are the HPV genotypes associated with human cancers, are multifunctional proteins that contribute to HPV-induced cancers in multiple ways. In this review, we describe the known activities of the MmuPV1-encoded E6 and E7 proteins and how those activities relate to the activities of HPV E6 and E7 oncoproteins encoded by mucosal and cutaneous high-risk HPV genotypes.

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Beta-Genus Human Papillomavirus 8 E6 Destabilizes the Host Genome by Promoting p300 Degradation

Cited by 12 publications

References 136 publications

Spatial tissue proteomics reveals distinct landscapes of heterogeneity in cutaneous papillomavirus‐induced keratinocyte carcinomas

Spatial tissue proteomics reveals distinct landscapes of heterogeneity in cutaneous papillomavirus‐induced keratinocyte carcinomas

Beta HPV Deregulates Double-Strand Break Repair

Molecular Mechanisms of MmuPV1 E6 and E7 and Implications for Human Disease

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