The HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity

Prathapam, Tulasiram; Kühne, Christian; Banks, Lawrence

doi:10.1038/sj.onc.1204960

Cited by 40 publications

(25 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lysis of cells and immunoblotting were carried out as described in ref. 36. mAbs 2-17 and EC10 were used to detect Src, and mAb4G10 (Upstate Biotechnology, Lake Placid, NY) was used to detect cellular phosphotyrosyl proteins.…”

Section: Methodsmentioning

confidence: 99%

Activated Src abrogates the Myc requirement for the G ₀ /G ₁ transition but not for the G ₁ /S transition

Prathapam

Tegen

Oskarsson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Section: Methodsmentioning

confidence: 99%

Activated Src abrogates the Myc requirement for the G ₀ /G ₁ transition but not for the G ₁ /S transition

Prathapam

Tegen

Oskarsson

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

“…Therefore, our results have added Skip-LEF-HDAC as one more Skip-mediated tripartite complex with three bipartite interactions, in addition to Skip-CBF1-NotchIC, Skip-CBF1-SMRT, Skip-VDR-RXR, and Skip-pRb-E7 (33,34,54,55). How Skip is involved dynamically in these conversion processes of Wnt signaling is not fully understood.…”

Section: Skip May Work As a Scaffold In ␤-Catenin-tcf-mediatedmentioning

confidence: 99%

Xenopus Skip Modulates Wnt/β-Catenin Signaling and Functions in Neural Crest Induction

Wang

Gao

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

The ␤-catenin-lymphoid enhancer factor (LEF) protein complex is the key mediator of canonical Wnt signaling and initiates target gene transcription upon ligand stimulation. In addition to ␤-catenin and LEF themselves, many other proteins have been identified as necessary cofactors. Here we report that the evolutionally conserved splicing factor and transcriptional co-regulator, SKIP/SNW/NcoA62, forms a ternary complex with LEF1 and HDAC1 and mediates the repression of target genes. Lossof-function studies showed that SKIP is obligatory for Wnt signaling-induced target gene transactivation, suggesting an important role of SKIP in the canonical Wnt signaling. Consistent with its involvement in ␤-catenin signaling, the C-terminally truncated forms of SKIP are able to stabilize ␤-catenin and enhance Wnt signaling. In Xenopus embryos, both overexpression and knockdown of Skip lead to reduced neural crest induction, consistent with down-regulated Wnt signaling in both cases. Our results indicate that SKIP is a novel component of the ␤-catenin transcriptional complex.

show abstract

“…E7 has been reported to bind to over 20 cellular proteins (2,8,11,47,55). These putative targets of E7 include multiple cell cycle regulators, such as the pocket proteins pRb, p107, and p130 and the cyclin-dependent kinase inhibitors p21 and p27 (47).…”

mentioning

confidence: 99%

“…These putative targets of E7 include multiple cell cycle regulators, such as the pocket proteins pRb, p107, and p130 and the cyclin-dependent kinase inhibitors p21 and p27 (47). Additional binding partners of E7 include transcription factors (c-Jun, IRF-1, and MPP2), transcriptional cofactors and chromatin-remodeling enzymes (TBP, TAF-110, Skip, p300, pCAF, and Mi2␤/histone deacetylase complexes), metabolic enzymes (M 2 pyruvate kinase and acid ␣-glucosidase), F-actin, and the proteasome (2,8,47,55). Thus, in vitro studies have suggested many possible mechanisms for E7 function.…”

mentioning

confidence: 99%

Examination of the pRb-Dependent and pRb-Independent Functions of E7 In Vivo

Balsitis

Dick

Lee

et al. 2005

J Virol

View full text Add to dashboard Cite

High-risk human papillomaviruses encode two oncogenes, E6 and E7, expressed in nearly all cervical cancers. Although E7 protein is best known for its ability to inactivate the retinoblastoma tumor suppressor protein, pRb, many other activities for E7 have been proposed in in vitro studies. Herein, we describe studies that allowed us to define unambiguously the pRb-dependent and -independent activities of E7 for the first time in vivo. In these studies, we crossed mice transgenic for human papillomavirus 16 E7 to knock-in mice genetically engineered to express a mutant form of pRb (pRb ⌬LXCXE ) that is selectively defective for binding E7. pRb inactivation was necessary for E7 to induce DNA synthesis and to overcome differentiation-dependent cell cycle withdrawal and DNA damage-induced cell cycle arrest. While most of E7's effects on epidermal differentiation were found to require pRb inactivation, a modest delay in terminal differentiation with resulting hyperplasia was observed in E7 mice on the Rb ⌬LXCXE mutant background. E7-induced p21 upregulation was also pRb dependent, and genetic Rb inactivation was sufficient to reproduce this effect. While E7-mediated p21 induction was partially p53 dependent, neither p53 nor p21 induction by E7 required p19 ARF . These data show that E7 upregulates the expression of p53 and p21 via pRb-dependent mechanisms distinct from the proposed p19-Mdm2 pathway. These results extend our appreciation of the importance of pRb as a relevant target for high-risk E7 oncoproteins.Human papillomaviruses (HPVs) are small DNA viruses and the causative agents of epithelial warts. The so-called "high-risk" HPVs, including HPV-16, infect the anogenital tract epithelium and are associated with almost all cases of cervical cancer, a leading cause of cancer mortality in women worldwide (64,69). Although the HPV genome usually exists extrachromosomally, many HPV-associated cancers contain HPV genomes integrated into the host DNA (20). These integrated genomes invariably contain intact viral E6 and E7 genes, and integration causes their increased expression (35). These data suggest that E6 and E7 contribute to the development of cervical cancers.HPV-16 E7 is a small nuclear phosphoprotein with potent transforming and tumorigenic properties. Coexpression of E6 and E7 is necessary and sufficient to transform primary human keratinocytes (48), and E7 acts robustly in a number of other in vitro transformation assays (6,44,52,62,63,65). E7-expressing cells exhibit genomic instability in culture (17,18,56,66,67) and have impaired cell cycle arrest responses to DNA damage (12,60). Additionally, expression of E7 in primary human keratinocytes or in transgenic mice results in abnormal centrosome synthesis, with associated multipolar mitoses and aneuploidy (3,(15)(16)(17). Previously, our laboratory generated mice transgenic for HPV-16 E7 under the control of the keratin 14 promoter, targeting E7 expression to the basal layer of stratified squamous epithelia such as the skin and cervical epithelium (30). Th...

show abstract

The HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity

Cited by 40 publications

References 31 publications

Activated Src abrogates the Myc requirement for the G ₀ /G ₁ transition but not for the G ₁ /S transition

Activated Src abrogates the Myc requirement for the G ₀ /G ₁ transition but not for the G ₁ /S transition

Xenopus Skip Modulates Wnt/β-Catenin Signaling and Functions in Neural Crest Induction

Examination of the pRb-Dependent and pRb-Independent Functions of E7 In Vivo

Contact Info

Product

Resources

About

The HPV-16 E7 oncoprotein binds Skip and suppresses its transcriptional activity

Cited by 40 publications

References 31 publications

Activated Src abrogates the Myc requirement for the G 0 /G 1 transition but not for the G 1 /S transition

Activated Src abrogates the Myc requirement for the G 0 /G 1 transition but not for the G 1 /S transition

Xenopus Skip Modulates Wnt/β-Catenin Signaling and Functions in Neural Crest Induction

Examination of the pRb-Dependent and pRb-Independent Functions of E7 In Vivo

Contact Info

Product

Resources

About

Activated Src abrogates the Myc requirement for the G ₀ /G ₁ transition but not for the G ₁ /S transition

Activated Src abrogates the Myc requirement for the G ₀ /G ₁ transition but not for the G ₁ /S transition