The Use of Intrinsic Disorder and Phosphorylation by Oncogenic Viral Proteins to Dysregulate the Host Cell Cycle Through Interaction with pRb
Abstract
:1. Introduction
2. LxCxE-Mediated pRb Interaction: Human Papillomavirus, Merkel Cell Polyomavirus, and BK Polyomavirus
2.1. Human Papillomavirus (HPV) E7 Directly Binds and Deactivates pRb Through LxCxE Motif
2.2. Polyomaviruses
2.3. Merkel Cell Polyomavirus (MCPyV) LTAg Protein Directly Binds and Deactivates pRb Through LxCxE Motif
2.4. BK Polyomavirus (BKPyV) LTAg Protein Directly Binds and Deactivates pRb Through LxCxE Motif
3. LxCxE-Mimic Strategies: Human T-Cell Lymphotropic Virus Type 1, Hepatitis C Virus, and Epstein–Barr Virus
3.1. Human T-Cell Lymphotropic Virus Type 1 (HTLV-1) Tax Directly Inhibits pRb Function Through LxCxE-Mimic Motif
3.2. Hepatitis C Virus (HCV) NS5B Directly Binds and Inhibits pRb Function Through LxCxE-Mimic Motif
3.3. Epstein–Barr Virus (EBV) EBNA-3C Directly Binds pRb Through a Potential LxCxE-Mimic Domain
4. LxCxE-Independent or Indirect pRb Interaction: Kaposi Sarcoma-Associated Herpesvirus and Hepatitis B Virus
4.1. Kaposi Sarcoma-Associated Herpesvirus (KSHV) LANA Directly Binds pRb Through Its C-Terminal Region
4.2. Hepatitis B Virus (HBV) HBx Indirectly Inhibits pRb Activity with the Potential for Direct Interaction
5. Conclusions
5.1. Viruses and Cancer Biology
5.2. Viral Detection and Prevention
6. Materials and Methods
6.1. PONDR® VLXT
6.2. NETPHOS-3.1
6.3. Protein Sequence Alignment
6.4. ACCESSION Numbers
Funding
Acknowledgments
Conflicts of Interest
References
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Virus | Abbreviation | Virus Family | Oncoprotein Causing pRb Dysregulation | Mode of pRb Interaction | Phorphorylation Site(s) Proximal to pRb Binding | Kinase |
---|---|---|---|---|---|---|
Human Papillomavirus | HPV | Papillomaviridae | E7 | LxCxE | S31/S32 | CK2 |
Merkel Cell Polyomavirus | MCPyV | Polyomaviridae | LTAg | LxCxE | S220 | Unknown |
BK Polyomavirus | BKPyV | Polyomaviridae | LTAg | LxCxE | S114 | CK2 * |
Human T-cell Lymphotropic Virus-1 | HTLV-1 | Retroviridae | Tax | LxCxE-mimic | S301/S302 | Unknown |
Hepatitis C Virus | HCV | Hepaviridae | NS5B | LxCxE-mimic | S326 | Akt kinase |
Epstein-Barr Virus | EBV (HHV-4) | Herpesviridae | EBNA-3C | LxCxE-mimic | S134 * | CK2 * |
Kaposi Sarcoma-associated Herpesvirus | KSHV (HHV-8) | Herpesviridae | LANA | LxCxE-Independent | Unknown | NA |
Hepatitis B Virus | HBV | Hepaviridae | HBx ? | Unknown | S25 ? | Unknown |
Virus | Abbreviation | Virus Family | Viral Oncoprotein | NCBI Accession | % Predicted Disorder |
---|---|---|---|---|---|
Human Papillomavirus | HPV | Papillomaviridae | E7 (HPV16) | NP_041326.1 | 27.6 |
Merkel Cell Polyomavirus | MCPyV | Polyomaviridae | LTAg | YP_009111421.1 | 32.7 |
BK Polyomavirus | BKPyV | Polyomaviridae | LTAg | PY_717940.1 | 24.5 |
Human T-cell Lyphotropic Virus-1 | HTLV-1 | Retrovridae | Tax | NP_957864.1 | 13 |
Hepatisis C Virus | HCV | Hepaviridae | NS5B RNA dependent RNA polymerase | CAB46677.1 NS5B (2420-3010 of the polypeptide) | 18.6 |
Epstein-Barr Virus | EBV (HHV-4) | Herpesviridae | EBNA-3C | YP_401671.1 | 66.8 |
Kaposi Sarcoma-associated Herpesvirus | KSHV (HHV-8) | Herpesviridae | LANA | YP_001129431.1 | 86.7 |
Hepatisis B Virus | HBV | Hepaviridae | HBx | ABG23459.1 | 30.5 |
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Kast-Woelbern, H.; Martinho, S.K.; Julio, K.T.; Vazzana, A.M.; Mandagie, A.E.; Jansma, A.L. The Use of Intrinsic Disorder and Phosphorylation by Oncogenic Viral Proteins to Dysregulate the Host Cell Cycle Through Interaction with pRb. Viruses 2025, 17, 835. https://doi.org/10.3390/v17060835
Kast-Woelbern H, Martinho SK, Julio KT, Vazzana AM, Mandagie AE, Jansma AL. The Use of Intrinsic Disorder and Phosphorylation by Oncogenic Viral Proteins to Dysregulate the Host Cell Cycle Through Interaction with pRb. Viruses. 2025; 17(6):835. https://doi.org/10.3390/v17060835
Chicago/Turabian StyleKast-Woelbern, Heidi, Sarah K. Martinho, Kayla T. Julio, Audrey M. Vazzana, Abbey E. Mandagie, and Ariane L. Jansma. 2025. "The Use of Intrinsic Disorder and Phosphorylation by Oncogenic Viral Proteins to Dysregulate the Host Cell Cycle Through Interaction with pRb" Viruses 17, no. 6: 835. https://doi.org/10.3390/v17060835
APA StyleKast-Woelbern, H., Martinho, S. K., Julio, K. T., Vazzana, A. M., Mandagie, A. E., & Jansma, A. L. (2025). The Use of Intrinsic Disorder and Phosphorylation by Oncogenic Viral Proteins to Dysregulate the Host Cell Cycle Through Interaction with pRb. Viruses, 17(6), 835. https://doi.org/10.3390/v17060835