The L2 Minor Capsid Protein of Low-Risk Human Papillomavirus Type 11 Interacts with Host Nuclear Import Receptors and Viral DNA

Bordeaux, Jennifer; Forte, Serene; Harding, E.; Darshan, Medha S.; Klucevsek, Kristin M.; Moroianu, Junona

doi:10.1128/jvi.00776-06

Cited by 31 publications

(29 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…KNβ3 also binds to and mediates nuclear transport of some viral proteins, including the L2 protein of HPV-16 and HPV-11. This interaction occurs via L2 nuclear localization signals, one in the N-terminus and one in the C-terminus [32,33]. We show that the 16E5-KNβ3 interaction primarily is mediated by 10 amino acids at the C-terminus of 16E5, since a C-terminal 16E5 (−10) deletion mutant is largely defective for binding KNβ3.…”

Section: Discussionmentioning

confidence: 92%

Karyopherin β3: A new cellular target for the HPV-16 E5 oncoprotein

Krawczyk

Hanover

Schlegel

et al. 2008

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Epidemiological and experimental studies have shown that high-risk human papillomaviruses (HPVs) are the causative agents of cervical cancer worldwide, and that HPV-16 is associated with more than half of these cases. In addition to the well-characterized E6 and E7 oncoproteins of HPV-16, recent evidence increasingly has implicated the HPV-16 E5 protein (16E5) as an important mediator of oncogenic transformation. Since 16E5 has no known intrinsic enzymatic activity, its effects on infected cells are most likely mediated by interactions with various cellular proteins and/ or its documented association with lipid rafts. In the present study, we describe a new cellular target that binds to 16E5 in COS cells and in stable human ectocervical cell lines. This target is karyopherin β3, a member of the nuclear import receptor family with critical roles in the nuclear import of ribosomal proteins and in the secretory pathway.

show abstract

Section: Discussionmentioning

confidence: 92%

Karyopherin β3: A new cellular target for the HPV-16 E5 oncoprotein

Krawczyk

Hanover

Schlegel

et al. 2008

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…L1/L2 aggregates, presumably, are the nucleation site for further capsid assembly, suggesting that L2 plays an important role in initial, regulated assembly of VLPs. Further linking the importance of L2 in native virion assembly is its ability to bind both L1 and DNA, suggesting that L2 is the mediator that facilitates assembly (Fligge et al, 2001;Fay et al, 2004;Bordeaux et al, 2006). Further, the analysis of in vitro assembly of L1/L2 VLPs has shown that L2 is incorporated into VLPs only when co-expressed with L1, or with L1 capsomeres .…”

Section: Structural Alterations Affecting Functionmentioning

confidence: 99%

“…These same experiments utilizing L2-deficient native virions depicted a role for L2 in DNA encapsidation and/or structural stability of the virions, since fewer DNase-resistant genomes were detected in the L2-deficient samples when compared with the wild-type native virions (Holmgren et al, 2005). Over the years, many publications have cited the appearance of viral and/or cellular factors that co-purify with native virions, such as E2, E4, E5, E7, and histones (Doorbar and Gallimore, 1987;Larsen et al, 1987;Heino et al, 2000;Fligge et al, 2001;Chromy et al, 2003Chromy et al, , 2006Gu et al, 2004;Bordeaux et al, 2006;Richards et al, 2006;Kondo et al, 2007;Bird et al, 2008;Buck et al, 2008).…”

Section: Structural Alterations Affecting Functionmentioning

confidence: 99%

“…that may either directly or indirectly affect the structure of the capsid (Doorbar and Gallimore, 1987;Larsen et al, 1987;Heino et al, 2000;Fligge et al, 2001;Chromy et al, 2003Chromy et al, , 2006Gu et al, 2004;Bordeaux et al, 2006;Richards et al, 2006;Kondo et al, 2007;Bird et al, 2008;Buck et al, 2008). Many other unknown viral and/or cellular factors are undoubtedly necessary for the proper assembly of native virions regarding regulation of redox states within the cell, proper cellular localization and initial interaction of capsid proteins, the correct formation/regulation of disulfide bonds, and regulation of capsid protein expression.…”

Section: Structural Alterations Affecting Functionmentioning

confidence: 99%

“…The L2/ genome complex may then interact with syntaxin 18, which ferries the complex to a perinuclear site (Bossis et al, 2005;Richards et al, 2006;Laniosz et al, 2008). L2 may then translocate the genome into the nucleus through its NLS (Fay et al, 2004;Bordeaux et al, 2006). Once in the nucleus, a sophisticated cascade of viral gene expression occurs which serves to maintain a minimum number of viral DNA copies per cell (Doorbar, 2005).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Replication and Assembly of Human Papillomaviruses

Conway

Meyers²

2009

J Dent Res

119

101

View full text Add to dashboard Cite

Human papillomaviruses (HPVs) are small dsDNA tumor viruses, which are the etiologic agents of most cervical cancers and are associated with a growing percentage of oropharyngeal cancers. The HPV capsid is non-enveloped, having a T=7 icosahedral symmetry formed via the interaction among 72 pentamers of the major capsid protein, L1. The minor capsid protein L2 associates with L1 pentamers, although it is not known if each L1 pentamer contains a single L2 protein. The HPV life cycle strictly adheres to the host cell differentiation program, and as such, native HPV virions are only produced in vivo or in organotypic "raft" culture. Research producing synthetic papillomavirus particles-such as virus-like particles (VLPs), papillomavirus-based gene transfer vectors, known as pseudovirions (PsV), and papillomavirus genome-containing quasivirions (QV)-has bypassed the need for stratifying and differentiating host tissue in viral assembly and has allowed for the rapid analysis of HPV infectivity pathways, transmission, immunogenicity, and viral structure.

show abstract

The Karyopherin proteins, Crm1 and Karyopherin β1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation

Watt

Maske

Hendricks

et al. 2009

Intl Journal of Cancer

246

237

View full text Add to dashboard Cite

The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest they are important in nuclear envelope component assembly, mitosis and replication. Since these are all critical cellular functions, alterations in the expression of the Karyopherins may have an impact on the biology of cancer cells. In this study, we examined the expression of the Karyopherins, Crm1, Karyopherin b1 (Kpnb1) and Karyopherin a2 (Kpna2), in cervical tissue and cell lines. The functional significance of these proteins to cancer cells was investigated using individual siRNAs to inhibit their expression. Microarrays, quantitative RT-PCR and immunofluorescence revealed significantly higher expression of Crm1, Kpnb1 and Kpna2 in cervical cancer compared to normal tissue. Expression levels were similarly elevated in cervical cancer cell lines compared to normal cells, and in transformed epithelial and fibroblast cells. Inhibition of Crm1 and Kpnb1 in cancer cells significantly reduced cell proliferation, while Kpna2 inhibition had no effect. Noncancer cells were unaffected by the inhibition of Crm1 and Kpnb1. The reduction in proliferation of cancer cells was associated with an increase in a subG1 population by cell cycle analysis and Caspase-3/7 assays revealed increased apoptosis. Crm1 and Kpnb1 siRNA-induced apoptosis was accompanied by an increase in the levels of growth inhibitory proteins, p53, p27, p21 and p18. Our results demonstrate that Crm1, Kpnb1 and Kpna2 are overexpressed in cervical cancer and that inhibiting the expression of Crm1 and Kpnb1, not Kpna2, induces cancer cell death, making Crm1 and Kpnb1 promising candidates as both biomarkers and potential anticancer therapeutic targets. ' 2008 Wiley-Liss, Inc.Key words: cervical cancer; nuclear transport proteins; Crm1; Karyopherin b1; Karyopherin a2Cervical cancer is the second most common cancer among women worldwide, 1 with nearly 80% of cases occurring in developing countries. 2 The primary risk factor in the development of the disease is infection with the Human Papillomavirus (HPV), 3,4 and more than 90% of cervical cancers carry high-risk HPV DNA. 4,5 The HPV E6 and E7 oncoproteins are responsible for cancer development, and evidence has shown that they alone are sufficient to immortalize human foreskin keratinocytes. 6 Their continued expression is essential for maintaining the transformed state. 6 HPV E6 and E7 promote cellular transformation by binding to and blocking the functions of the cell cycle regulatory proteins, p53 and pRb, respectively. 7,8 Prophylactic vaccines against lowrisk (HPV6, 11) and high-risk (HPV16 and 18) HPV types have recently been developed. 9 They rely on the vaccination of women before exposure to the virus; hence, their benefit to women already infected with HPV is still unclear, as well as their benefit to women infected with HPV types other than HPV6, 11, 16 and 18.Although the high-risk HPV proteins are the causative agents behind cervical cance...

show abstract

The L2 Minor Capsid Protein of Low-Risk Human Papillomavirus Type 11 Interacts with Host Nuclear Import Receptors and Viral DNA

Cited by 31 publications

References 21 publications

Karyopherin β3: A new cellular target for the HPV-16 E5 oncoprotein

Karyopherin β3: A new cellular target for the HPV-16 E5 oncoprotein

Replication and Assembly of Human Papillomaviruses

The Karyopherin proteins, Crm1 and Karyopherin β1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation

Contact Info

Product

Resources

About