UBE2O reduces the effectiveness of interferon-α via degradation of IFIT3 in hepatocellular carcinoma.
Cell Death Dis
; 14(12): 854, 2023 12 21.
Article
in En
| MEDLINE
| ID: mdl-38129382
ABSTRACT
Interferon (IFN) exerts its effects through interferon-stimulated genes (ISGs), but its efficacy is limited by interferon resistance, which can be caused by the ubiquitination of key proteins. UBE2O was initially identified as a promising therapeutic target based on data from the TCGA and iUUCD 2.0 databases. Through the inhibition of UBE2O, interferon α/ß signaling and overall interferon signaling were activated. Integrating data from proteomic, mass spectrometry, and survival analyses led to the identification of IFIT3, a mediator of interferon signaling, as a ubiquitination substrate of UBE2O. The results of in vitro and in vivo experiments demonstrated that the knockdown of UBE2O can enhance the efficacy of interferon-α by upregulating IFIT3 expression. K236 was identified as a ubiquitination site in IFIT3, and the results of rescue experiments confirmed that the effect of UBE2O on interferon-α sensitivity is dependent on IFIT3 activity. ATO treatment inhibited UBE2O and increased IFIT3 expression, thereby increasing the effectiveness of interferon-α. In conclusion, these findings suggest that UBE2O worsens the therapeutic effect of interferon-α by targeting IFIT3 for ubiquitination and degradation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Hepatocellular
/
Liver Neoplasms
Limits:
Humans
Language:
En
Journal:
Cell Death Dis
Year:
2023
Document type:
Article
Country of publication:
Reino Unido