The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Cutaneous β-human papillomavirus E6 proteins bind Mastermind-like coactivators and repress Notch signaling
Open accessAbstract
The Notch signaling pathway is a key determinant in keratinocyte differentiation and growth cycle arrest, and has been reported to have a tumor suppressor function in skin. The papillomavirus life cycle is intricately linked to the differentiation status of keratinocytes. Papillomaviruses are associated with benign proliferative epithelial lesions in their respective hosts. Although human papillomaviruses (HPVs) associated with genital tract lesions have been extensively studied, studies of the cutaneous HPVs are more limited. In particular, it is well established that the E6 proteins of high-risk HPVs of the α-genus such as HPV16 and HPV18 mediate the degradation of p53 by its association with the ubiquitin ligase E6AP. In contrast, less is known about the cellular activities of the cutaneous HPVs of the β-genus. By using an unbiased proteomic approach, we identify MAML1 and other members of the Notch transcription complex as high-confidence cellular interacting proteins of E6 proteins of the β-genus HPVs and of the bovine papillomavirus type 1 associated with cutaneous fibropapillomas. We show that bovine papillomavirus type 1 and β-HPV E6 repress Notch transcriptional activation, and that this repression is dependent on an interaction with MAML1. Finally, we show that the expression levels of endogenous Notch target genes are repressed by β-HPV E6 proteins. These findings elucidate a mechanism of viral antagonism of Notch signaling, and suggest that Notch signaling is an important epithelial cell pathway target for the β-HPVs.
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In the citing paper
“the E6 protein of genus alpha HPV binds specifically to the cellular E6AP protein”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [69]
In the citing paper
“Both virus–host interactions are mediated by a similar motif in the cellular protein”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [69]
In the citing paper
“while that of the genus beta HPV binds specifically to cellular MAML1.”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [69]
In the citing paper
“and may be responsible for the different cell type-specific tropisms of the two genera”
From Proteomic approaches to uncovering virus–host protein interactions during the progression of viral infection (2016) · cites this paper as [69]
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Cites
Notch Signaling: Cell Fate Control and Signal Integration in Development
Artavanis-Tsakonas, S., Rand, M. D., & Lake, R. J. (1999) · Science · doi:10.1126/science.284.5415.770 · Cited by 5,909
Activating Mutations of NOTCH1 in Human T Cell Acute Lymphoblastic Leukemia
Weng, A. P., Ferrando, A. A., Lee, W., Morris, J. P., Silverman, L. B., Sanchez-Irizarry, C., Blacklow, S. C., Look, A. T., & Aster, J. C. (2004) · Science · doi:10.1126/science.1102160 · Cited by 2,706
Self-citationThe Mutational Landscape of Head and Neck Squamous Cell Carcinoma
Stransky, N., Egloff, A. M., Tward, A. D., Kostic, A. D., Cibulskis, K., Sivachenko, A., Kryukov, G. V., Lawrence, M. S., Sougnez, C. L., McKenna, A., et al. (2011) · Science · doi:10.1126/science.1208130 · Cited by 2,541
Exome Sequencing of Head and Neck Squamous Cell Carcinoma Reveals Inactivating Mutations in NOTCH1
Agrawal, N., Frederick, M. J., Pickering, C. R., Bettegowda, C., Chang, K., Li, R. J., Fakhry, C., Xie, T., Zhang, J., Wang, J., et al. (2011) · Science · doi:10.1126/science.1206923 · Cited by 1,697
Defining the Human Deubiquitinating Enzyme Interaction Landscape
Sowa, M. E., Bennett, E. J., Gygi, S. P., & Harper, J. W. (2009) · Cell · doi:10.1016/j.cell.2009.04.042 · Cited by 1,523
Self-citationSignalling downstream of activated mammalian Notch
Jarriault, S., Brou, C., Logeat, F., Schroeter, E. H., Kopan, R., & Israël, A. (1995) · Nature · doi:10.1038/377355a0 · Cited by 1,390
Dickson, M. A., Hahn, W. C., Ino, Y., Ronfard, V., Wu, J. Y., Weinberg, R. A., Louis, D. N., Li, F. P., & Rheinwald, J. G. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.4.1436-1447.2000 · Cited by 1,104
Notch1 functions as a tumor suppressor in mouse skin
Nicolas, M., Wolfer, A., Raj, K., Kummer, J. A., Mill, P., van Noort, M., Hui, C., Clevers, H. C., Dotto, G. P., & Radtke, F. (2003) · Nature Genetics · doi:10.1038/ng1099 · Cited by 969
Huibregtse, J. M., Scheffner, M., & Howley, P. M. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb04990.x · Cited by 879
Self-citationNotch signaling is a direct determinant of keratinocyte growth arrest and entry into differentiation
Rangarajan, A., Talora, C., Okuyama, R., Nicolas, M., Mammucari, C., Oh, H., Aster, J. C., Krishna, S., METZGER, D., Chambon, P., et al. (2001) · The EMBO Journal · doi:10.1093/emboj/20.13.3427 · Cited by 867
Self-citation
Flagged first, then by citations
Research works printed but not linked: 6
- PM Howley, DR Lowy, Papillomaviruses. Fields Virology, eds D Knipe, P Howley (Lippincott Williams and Wilkins, 5th Ed, Philadelphia), pp. 2299–2354 (2007).
- PM Howley, DR Lowy, Papillomaviruses. Fields Virology, eds D Knipe, P Howley (Lippincott Williams and Wilkins, 5th Ed, Philadelphia), pp. 2299–2354 (2007).
- 10.1016/S1367-5931(02)00346-0 · DOI
- 10.1093/emboj/20.13.3427 · DOI
- 10.1016/j.cell.2009.04.042 · DOI
- 10.1038/ng1099 · DOI
Cited by
Sorted by citations
Items 101–132 of 132
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Sominsky, S., Shterzer, N., Jackman, A., Shapiro, B., Yaniv, A., & Sherman, L. (2017) · Virology · doi:10.1016/j.virol.2017.05.020 · Cited by 9
Skelin, J., Đukić, A., Filić, V., Hufbauer, M., Akgũl, B., Thomas, M., Banks, L., & Tomaić, V. (2023) · Journal of Medical Virology · doi:10.1002/jmv.28624 · Cited by 8
The Actinic Keratosis Virome: Can We Prevent Squamous Cell Carcinoma with a Vaccine?
Frazer, I. H. (2014) · Current problems in dermatology · doi:10.1159/000366532 · Cited by 8
Transcription Properties of Beta-HPV8 and HPV38 Genomes in Human Keratinocytes
Rehm, T. M., Straub, E., Forchhammer, S., Leiter, U., Iftner, T., & Stubenrauch, F. (2022) · Journal of Virology · doi:10.1128/jvi.01498-22 · Cited by 7
Brimer, N., Wade, R., & Pol, S. V. (2014) · Journal of Virology · doi:10.1128/jvi.00552-14 · Cited by 7
MmuPV1 E6 induces cell proliferation and other hallmarks of cancer
Romero-Masters, J. C., Muehlbauer, L. K., Hayes, M., Grace, M. R., Shishkova, E., Coon, J. J., Münger, K., & Lambert, P. F. (2023) · mBio · doi:10.1128/mbio.02458-23 · Cited by 5
HPV8-induced STAT3 activation led keratinocyte stem cell expansion in human actinic keratoses
Morgan, H. J., Olivero, C., Shorning, B. Y., Gibbs, A., Phillips, A., Ananthan, L., Lim, A. X. H., Martuscelli, L., Borgogna, C., Andrea, M. D., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.177898 · Cited by 7
Reply to: Beta human papillomaviruses and skin cancer
Strickley, J. D., Messerschmidt, J. L., Jenson, A. B., Joh, J. J., & Demehri, S. (2020) · Nature · doi:10.1038/s41586-020-3024-z · Cited by 6
Lim, J., Straub, E., Stubenrauch, F., Iftner, T., Schindler, M., & Simon, C. (2022) · Scientific Reports · doi:10.1038/s41598-022-06922-0 · Cited by 5
Zema, S., Fazio, F. D., Pelullo, M., Savino, S. D., Cerbelli, B., Leopizzi, M., Magno, L. D., Nicoletti, C., Peruzzi, G., D’Andrea, D., et al. (2025) · Cell Death and Differentiation · doi:10.1038/s41418-025-01613-5 · Cited by 4
Weimer, K. (2024) · Tumour Virus Research · doi:10.1016/j.tvr.2024.200311 · Cited by 4
Moreno, R., Buehler, D. G., & Lambert, P. F. (2022) · Viruses · doi:10.3390/v14081751 · Cited by 4
The transforming properties of human papillomavirus oncoproteins
Grce, M., Sabol, I., & Gašperov, N. M. (2012) · Institutional Repository of the Ruđer Bošković Institute (Ruđer Bošković Institute) · Cited by 4
Taute, S., Böhnke, P., Sprissler, J., Buchholz, S., Hufbauer, M., Akgũl, B., & Steger, G. (2019) · Cells · doi:10.3390/cells8030244 · Cited by 4
Vella, L., Sternjakob, A., Lohse, S., Fingerle, A., Sperling, T., Wickenhauser, C., Stöckle, M., VOGT, T. M., Roemer, K., Ołdak, M., et al. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1336492 · Cited by 2
Lim, J., Frecot, D. I., Stubenrauch, F., Iftner, T., & Simon, C. (2022) · Virology · doi:10.1016/j.virol.2022.08.014 · Cited by 2
Squamous Cell Carcinoma and Its Rare Variant, Carcinoma Cuniculatum: Insights and Case Studies
Knecht-Gurwin, K., Stefaniak, A. A., Chlebicka, I., Matusiak, Ł., Woźniak, Z., & Szepietowski, J. C. (2025) · Cancers · doi:10.3390/cancers17071217 · Cited by 2
Beta Human Papillomavirus and Merkel Cell Polyomavirus in Skin Neoplasms
Lv, Q., Ye, Y., Li, L., Li, F., Wu, Y.-L., & Jiang, M. (2020) · International Journal of Dermatology and Venereology · doi:10.1097/jd9.0000000000000087 · Cited by 2
Tian, Z., Li, T., Fan, Y., Li, J., Luo, S., Cao, W., Pan, Q., & Hu, X. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1590538 · Cited by 1
Pathophysiology of cutaneous commensal human papillomaviruses
Bruyère, D., Delahaye, T., Nikkels, A., & Herfs, M. F. (2026) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2026.02.011 · Cited by 1
Mutational Profile of HPV-Positive HNSCC
Li, H., & Grandis, J. R. (2015) · Springer eBooks · doi:10.1007/978-3-319-21100-8_8 · Cited by 1
McLaughlin-Drubin, M. E., & Munger, K. L. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.00007-6 · Cited by 1
Skin cancer in organ transplant recipients : histopathological and epidemiological studies
Krynitz, B. (2015) · Figshare
Rogers, J. M., Guo, B., Egan, E. D., Aster, J. C., Adelman, K., & Blacklow, S. C. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.13.905612
Self-citationThe HPV viral regulatory mechanism of TLRs and the Related treatments for HPV-Associated CancersPreprint
Deng, S., Qi, S.-Y., Yu, K., & Lian, Z. (2023) · doi:10.22541/au.169580703.36248267/v1
Recent Topics of Human Papillomavirus and Cervical Cancer
Kukimoto, I. (2024) · Comprehensive gynecology and obstetrics · doi:10.1007/978-981-99-9396-3_1
Santos, L. A. B. D. O., Feitosa, T. D. A. L., & Batista, M. V. D. A. (2024) · Genetics and Molecular Biology · doi:10.1590/1678-4685-gmb-2023-0346
Brancaccio, R. N. (2020) · theses.fr (ABES) · doi:10.70675/b9d29e13z941fz4bdezbed3zcb7b5813f658
Vizcarra-Ramos, S., García-Gómez, J., Rojo-Contreras, W., Jave‐Suárez, L. F., & Aguilar‐Lemarroy, A. (2026) · Pathogens · doi:10.3390/pathogens15101048
Metadata
- Authors
- Tan, M. J. A., White, E. A., Sowa, M. E., Harper, J. W., Aster, J. C., & Howley, P. M.
- Affiliations
- Harvard University (US)
- Departments of Microbiology and Immunobiology and
- Brigham and Women's Hospital (US)
- Corresponding author
- Howley, Peter M.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-04-30
- Volume
- 109
- Issue
- 23
- Pages
- E1473-80
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3384212
- OpenAlex
- W2020553511
- Cited by
- 132
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 9 · 2022: 6 · 2021: 8 · 2020: 13 · 2019: 10 · 2018: 7 · 2017: 17 · 2016: 9 · 2015: 10 · 2014: 13 · 2013: 11 · 2012: 6
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brigham and Women's Hospital
- National Institutes of Health
- National Cancer Institute (P01 CA 50661, RC1CA145188, P01CA050661)
- National Institute of General Medical Sciences (R01GM054137)
- National Institute of Allergy and Infectious Diseases (F32AI080075)
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- E6 oncoprotein, Notch signaling, MAML1, bovine papillomavirus type 1, keratinocyte differentiation, Notch target genes
- MeSH terms
- Animals, Cell Line, DNA-Binding Proteins, Humans, Luciferases, Oncogene Proteins, Viral, Plasmids, Transcription Factors, Transfection, Blotting, Western, Signal Transduction, Proteomics, Mice, Receptors, Notch, Betapapillomavirus, Real-Time Polymerase Chain Reaction
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