Cutaneous papillomavirus E6 oncoproteins associate with MAML1 to repress transactivation and NOTCH signaling
Open accessAbstract
Papillomavirus E6 oncoproteins associate with LXXLL motifs on target cellular proteins to alter their function. Using a proteomic approach, we found the E6 oncoproteins of cutaneous papillomaviruses Bovine Papillomavirus Type 1 (BPV-1) E6 and human papillomavirus (HPV) types 1 and 8 (1E6 and 8E6) associated with the MAML1 transcriptional co-activator. All three E6 proteins bind to an acidic LXXLL motif at the carboxy-terminus of MAML1 and repress transactivation by MAML1. MAML1 is best known as the co-activator and effector of NOTCH-induced transcription, and BPV-1 E6 represses synthetic NOTCH-responsive promoters, endogenous NOTCH-responsive promoters, and is found in a complex with MAML1 in stably transformed cells. BPV-1-induced papillomas show characteristics of repressed NOTCH signal transduction, including suprabasal expression of integrins, talin and basal type keratins, and delayed expression of the NOTCH-dependent HES1 transcription factor. These observations give rise to a model whereby papillomavirus oncoproteins, including BPV-1 E6, and the cancer-associated HPV-8 E6 repress NOTCH-induced transcription, thereby delaying keratinocyte differentiation.
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The E6 protein of genus alpha HPV binds specifically to the cellular E6AP protein.
“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 [66]
The E6 protein of genus beta HPV binds specifically to cellular MAML1.
“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 [66]
Both virus-host interactions are mediated by a similar motif in the cellular protein.
“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 [66]
Both virus-host interactions may be responsible for the different cell type-specific tropisms of the two genera.
“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 [66]
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- Authors
- Brimer, N., Lyons, C., Wallberg, A. E., & Vande Pol, S. B.
- Affiliations
- University of Virginia (US)
- Karolinska Institutet (SE)
- Venue
- Oncogene
- Published
- 2012-01-16
- Volume
- 31
- Issue
- 43
- Pages
- 4639-4646
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC3330202
- OpenAlex
- W1985884010
- Cited by
- 133
- References
- 77
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 13 · 2022: 10 · 2021: 7 · 2020: 9 · 2019: 8 · 2018: 12 · 2017: 11 · 2016: 10 · 2015: 13 · 2014: 9 · 2013: 14 · 2012: 7
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (CA120352, CA08093, R01CA120352, R01CA134737)
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- MAML1, Notch signaling, LXXLL motif, transcriptional repression, bovine papillomavirus type 1, human papillomavirus type 1, Hes1, keratinocyte differentiation, integrins, talin, papilloma formation
- MeSH terms
- DNA-Binding Proteins, Humans, Promoter Regions, Genetic, Skin, Transcription Factors, Viral Proteins, Signal Transduction, Transcriptional Activation, Papillomaviridae, Receptors, Notch
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