REVIEW article
Front. Microbiol.
Sec. Virology
Decoding Microbial Carcinogenic Strategies: Ubiquitination and SUMO Modification
Provisionally accepted
- 1First Affiliated Hospital of Gannan Medical University, Nanchang, China
- 2Gannan Medical University, Ganzhou, China
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Abstract: Carcinogenic microorganisms (including viruses, bacteria, fungi, etc.) disrupt cellular homeostasis to drive tumourigenesis by hijacking the host ubiquitin-proteasome system (UPS) and SUMOylation networks, with oncogenic viruses representing the core agents of this regulatory mechanism. Specifically: - Human papillomavirus (HPV) E6 protein binds E3 ubiquitin ligase E6AP to mediate ubiquitin-mediated degradation of tumour suppressor p53, thereby disabling cell cycle surveillance; The HBx protein of hepatitis B virus (HBV) evades its own ubiquitin-mediated degradation by inhibiting the activity of the E3 ligase SIAH1, while simultaneously upregulating DNA methyltransferases to disrupt host epigenetics; The core protein of hepatitis C virus (HCV) induces methylation of the E6AP promoter, blocking its own ubiquitin-mediated degradation to maintain oncogenic activity; Epstein-Barr virus (EBV) LMP1 activates IRF7 via K63-linked ubiquitination, sustaining NF-xB pathway activation to promote proliferation; Kaposi's sarcoma-associated herpesvirus (KSHV) K3 protein mediates MHC-I molecule ubiquitination-dependent endocytosis, achieving immune evasion. Furthermore, non-viral microorganisms such as Helicobacter pylori CagA and aflatoxin A also participate in carcinogenesis by regulating the UPS/SUMO system. In summary, targeted modulation of the UPS/SUMO system constitutes a core oncogenic strategy for carcinogenic microorganisms (particularly viruses), providing molecular targets for 2 precision cancer therapy.
Keywords: Carcinogenic microorganisms, Infection-associated carcinogenesis, targeted therapies, Tumorigenesis mechanisms, Ubiquitin-SUMO axis
Received: 07 Oct 2025; Accepted: 08 Dec 2025.
Copyright: © 2025 Liu, Zeng, Lyu and Huang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dandan Huang
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