The E1^E4 Protein of Human Papillomavirus Interacts with the Serine-Arginine-Specific Protein Kinase SRPK1

Bell, Ian M.; Martin, Ashley; Roberts, Sally

doi:10.1128/jvi.02609-06

Cited by 35 publications

(46 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…hpV viral early proteins are involved in a variety of intracellular processes, including splicing. it has previously been demonstrated by Bell et al that hpV E4 protein interacts with SR-specific kinase SRPK1, which consequently impairs spliceosome assembly (27). In addition, Bodaghi et al showed that hpV16 proteins E2 and E6 are rna-binding proteins and may affect splicing both by binding directly to pre-mrna and by interacting with splicing factors (28).…”

Section: Discussionmentioning

confidence: 99%

IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions

Koczorowska

Kwaśniewska

Goździcka-Józefiak

2010

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. human papillomavirus (hpV) plays a crucial role in cervical cancer etiology. however, not all hpV-infected women develop cancer, indicating that additional cellular factors facilitate carcinogenesis. the aim of this study was to analyze the expression profile of insulin-like growth factor 1 (iGF1) isoforms in the context of FOx2, Sp1 and iGF1 receptor (iGF1r) expression during hpV-dependent cervical carcinogenesis. One hundred and nine epithelial tissue samples from women with pre-cancerous and cancer lesions of the cervix were analyzed. HPV DNA was identified by pcr, and real-time pcr was used to quantify the expression levels of the analyzed genes. all IGF1 mrna splicing isoforms were up-regulated in pre-cancerous cells, and a shift in the balance towards mitogenic iGF1Eb was observed in the cancer samples. IGF1 expression was controlled mainly by the p1 promoter, and an increase in p2 usage was observed in the cancer. correlations between IGF1 mrna splicing isoforms and the FOx2 splicing factor, as well as p1/p2 activity and Sp1 transcription factor expression levels were detected. no correlation was observed between the expression of iGF1 and its receptor iGF1r. Our results suggest that iGF1, in particular its splicing profile, may be an additional prognostic factor in cervical carcinogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions

Koczorowska

Kwaśniewska

Goździcka-Józefiak

2010

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…Arginine 45 lies in a region of HPV1 E4 that is rich in basic amino acids, and indeed, similar (but not identical) regions are to be found in E4 proteins of types with a tropism dissimilar to that of HPV1, such as HPV16 and -18, which have a preference for epithelia of the oral and anogenital tracts (1). The basic region of HPV16 E4 forms part of the G 2 arrest domain (5), but in HPV1, E4 is not a required element of the G 2 arrest function, nor do these regions contribute to the interaction with the keratin cytoskeleton (25,27).…”

Section: Discussionmentioning

confidence: 99%

“…The sequence integrity of plasmid inserts was verified by bidirectional DNA sequencing. The substitution-containing proteins E4R45A, E4R47A, and E4R48A are described elsewhere (1).…”

Section: Methodsmentioning

confidence: 99%

“…A potent G 2 arrest function is a conserved function of E4 proteins between HPV types with dissimilar tropism, and it is thought that division arrest of infected cells might be necessary to support efficient viral DNA amplification (5,13,19). E4 inclusion bodies found in the cytoplasm of cells of HPV1 skin warts contain the kinase SRPK1, a binding partner of E1^E4 proteins, which is associated with regulating the function of splicing factors (1). Sequestration of SRPK1 by E4 could be an HPV mechanism to regulate expression of viral late transcripts at the late stages of the replication cycle (1).…”

mentioning

confidence: 99%

“…E4 inclusion bodies found in the cytoplasm of cells of HPV1 skin warts contain the kinase SRPK1, a binding partner of E1^E4 proteins, which is associated with regulating the function of splicing factors (1). Sequestration of SRPK1 by E4 could be an HPV mechanism to regulate expression of viral late transcripts at the late stages of the replication cycle (1). Late in the infectious cycle, the E4 protein may also act to diminish the integrity of the keratinocyte by disrupting the keratin cytoskeleton and cornified envelope formation and inducing apoptosis through alteration of mitochondrial function to facilitate egress of the newly formed HPV virions (3,6,24,26).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Identification of an Arginine-Rich Motif in Human Papillomavirus Type 1 E1^E4 Protein Necessary for E4-Mediated Inhibition of Cellular DNA Synthesis In Vitro and in Cells

Roberts

Kingsbury

Stoeber

et al. 2008

J Virol

Self Cite

View full text Add to dashboard Cite

Human papillomaviruses (HPVs) are a large group (Ͼ100 types) of small DNA viruses that replicate in keratinocytes of squamous epithelia. HPV infections produce hyperproliferative warts that are in most instances benign. A small subset of HPV types, however, form lesions on the skin, and on the oropharyngeal-and anogenital-tract mucosae, that have a significant risk of malignant transformation. The most common cancer attributable to infection with the high-risk HPV types is cancer of the uterine cervix (35). Despite the differences in pathogenesis between virus types, their life cycles are similar (10), beginning with infection of keratinocytes within the basal cell compartment of squamous epithelia. Here the HPV genome is replicated as a low-copy-number (50 to 100 copies per cell) episome in synchrony with the replication of the host cell genome, a process that requires HPV E1 and E2 functions. HPV early proteins E6 and E7 act to expand the population of HPV-infected keratinocytes once they migrate up from the basal layer, by stimulating cell cycle entry and cell survival. The virus then utilizes the host cell's replication machinery, which has been activated in these cells, to amplify the HPV DNA to many thousands of copies per cell during the vegetative stage of the life cycle. Finally, the capsid proteins L1 and L2 are produced, and new progeny are assembled in the most superficial cells prior to their release from the highly differentiated squames.A major protein produced during the HPV life cycle is the E4 protein. It is expressed as an E1^E4 fusion protein from spliced transcripts formed between the N terminus of the E1 open reading frame and almost the complete open reading frame of E4 (21). The precise function of E4 has not been defined, but loss of expression of the full-length E1^E4 polypeptide has a severe adverse effect on viral genome amplification of HPV type 16 (HPV16), HPV18, and HPV31 following introduction of mutant genomes unable to support E1^E4 expression into keratinocytes and subsequent induction of cellular differentiation (20,38,39). Failure to complete the vegetative stage of the virus life cycle is also the outcome of loss of E1^E4 expression in rabbit papillomas induced by a mutant cottontail rabbit papillomavirus genome (22). These studies suggest that E4 function is necessary for efficient vegetative replication of the virus, a hypothesis supported by coincidence between onset of viral genome amplification and induction of high-level E4 production in natural papillomavirus infections (23).Examination of E4 activity in epithelial cell cultures has revealed diverse biological actions that perhaps imply a multifunctional role for this viral protein in the virus life cycle. These include disruption of ND10 body organization, which might be required for viral DNA replication, either by organization of viral replication centers or by inactivation of a host

show abstract

Programmable protein arrays for immunoprofiling HPV‐associated cancers

et al. 2016

View full text Add to dashboard Cite

Over 600 000 cancers each year are attributed to the human papillomavirus (HPV), including cervical, anogenital and oropharyngeal cancers (OPC). A key challenge in understanding HPV immunobiology is the diversity of oncogenic HPV types and the need for multiplexed display of HPV antigens to measure antibody responses. We have generated custom HPV protein microarrays displaying 98 proteins as C-terminal GST fusion proteins, representing eight antigens of two low-risk HPV types (HPV6 and 11) and ten oncogenic high-risk HPV types (HPV16, 18, 31, 33, 35, 39, 45, 51, 52 and 58). We demonstrate robust and reproducible protein expression of 96/98 of the antigens using a human cell lysate expression system. The target epitopes and specificities of four monoclonal antibodies were identified. Using sera from ten patients with newly diagnosed OPC and ten controls, we demonstrate specific IgG seroreactivity to HPV16 E1, E2, and E7 (a fold increase of 1.52, 2.19 and 1.35 in cases vs. controls, respectively, all p < 0.005), confirming our prior data on an ELISA platform. We also detect HPV52 E7 Abs in serum from a patient with cervical cancer. The HPV protein array has potential for rapid identification of serologic responses to 12 HPV types.

show abstract

The E1^E4 Protein of Human Papillomavirus Interacts with the Serine-Arginine-Specific Protein Kinase SRPK1

Cited by 35 publications

References 60 publications

IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions

IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions

Identification of an Arginine-Rich Motif in Human Papillomavirus Type 1 E1^E4 Protein Necessary for E4-Mediated Inhibition of Cellular DNA Synthesis In Vitro and in Cells

Programmable protein arrays for immunoprofiling HPV‐associated cancers

Contact Info

Product

Resources

About