Decoding microbial carcinogenic strategies: ubiquitination and SUMO modification
Yue Liu1,2, Xianghai Zeng1,2, Zhimai Lyu2
1School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, China.
Abstract:
Carcinogenic microorganisms (including viruses, bacteria, fungi, etc.) disrupt cellular homeostasis to drive tumorigenesis 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 tumor 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 precision cancer therapy.
Insights
Carcinogenic microorganisms, especially viruses, hijack the host ubiquitin-proteasome system (UPS) and SUMOylation networks to cause cancer. Targeting these pathways offers new precision cancer therapy strategies.
Area of Science:
- Molecular Biology
- Oncology
- Microbiology
Background:
- Carcinogenic microorganisms disrupt cellular homeostasis to promote tumorigenesis.
- Oncogenic viruses, bacteria, and fungi exploit host regulatory networks.
- The ubiquitin-proteasome system (UPS) and SUMOylation are key cellular processes implicated in cancer.
Purpose of the Study:
- To elucidate the mechanisms by which carcinogenic microorganisms manipulate the UPS and SUMOylation networks.
- To highlight the role of oncogenic viruses in hijacking these host systems for tumor promotion.
- To identify potential molecular targets for precision cancer therapy.
Main Methods:
- Review of existing literature on microbial carcinogenesis and host UPS/SUMOylation pathways.
- Analysis of specific viral proteins (e.g., HPV E6, HBV HBx, HCV core, EBV LMP1, KSHV K3) and their interactions with UPS/SUMOylation components.
- Examination of non-viral microbial factors (e.g., H. pylori CagA, aflatoxin A) involved in UPS/SUMOylation regulation.
Main Results:
- Oncogenic viruses utilize diverse strategies to modulate UPS/SUMOylation, including protein degradation, epigenetic alterations, and immune evasion.
- HPV E6 targets p53 degradation; HBV HBx inhibits E3 ligase SIAH1; HCV core blocks its degradation; EBV LMP1 activates NF-xB; KSHV K3 mediates immune evasion.
- Non-viral agents like H. pylori CagA and aflatoxin A also regulate these critical cellular pathways.
Conclusions:
- Targeted modulation of the UPS/SUMO system is a central oncogenic strategy employed by carcinogenic microorganisms.
- Understanding these microbial hijacking mechanisms provides crucial insights for developing novel precision cancer therapies.
- The UPS/SUMOylation network represents a promising therapeutic target for cancers associated with microbial infections.
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