SIAH2 suppresses c-JUN pathway by promoting the polyubiquitination and degradation of HBx in hepatocellular carcinoma.
J Cell Mol Med
; 28(11): e18484, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38842124
ABSTRACT
As an important protein encoded by hepatitis B virus (HBV), HBV X protein (HBx) plays an important role in the development of hepatocellular carcinoma (HCC). It has been shown that seven in absentia homologue 1 (SIAH1) could regulates the degradation of HBx through the ubiquitin-proteasome pathway. However, as a member of SIAH family, the regulatory effects of SIAH2 on HBx remain unclear. In this study, we first confirmed that SIAH2 could reduce the protein levels of HBx depending on its E3 ligase activity. Moreover, SIAH2 interacted with HBx and induced its K48-linked polyubiquitination and proteasomal degradation. Furthermore, we provided evidence that SIAH2 inhibits HBx-associated HCC cells proliferation by regulating HBx. In conclusion, our study identified a novel role for SIAH2 in promoting HBx degradation and SIAH2 exerts an inhibitory effect in the proliferation of HBx-associated HCC through inducing the degradation of HBx. Our study provides a new idea for the targeted degradation of HBx and may have great huge significance into providing novel evidence for the targeted therapy of HBV-infected HCC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nuclear Proteins
/
Trans-Activators
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Hepatitis B virus
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Carcinoma, Hepatocellular
/
Ubiquitin-Protein Ligases
/
Cell Proliferation
/
Viral Regulatory and Accessory Proteins
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Ubiquitination
/
Proteolysis
/
Liver Neoplasms
Limits:
Humans
Language:
En
Journal:
J Cell Mol Med
Journal subject:
BIOLOGIA MOLECULAR
Year:
2024
Type:
Article
Affiliation country:
China