# Decoding microbial carcinogenic strategies: ubiquitination and SUMO modification

## TL;DR

This paper explains how cancer-causing microbes, especially viruses, use the host's ubiquitin and SUMO systems to disrupt normal cell function and cause cancer.

## Contribution

The paper systematically decodes how various carcinogenic microorganisms exploit ubiquitination and SUMOylation to drive tumorigenesis.

## Key findings

- HPV E6 and HBV HBx proteins manipulate the ubiquitin system to degrade tumor suppressors or evade degradation.
- HCV core protein and EBV LMP1 alter ubiquitination to maintain oncogenic activity and promote cell proliferation.
- Non-viral agents like H. pylori CagA also use the UPS/SUMO system to contribute to cancer development.

## 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.