Ubiquitin E3 ligase β‐TrCP negatively regulates surface protein of hepatitis B virus

Abstract

Chronic hepatitis B (CHB) still cannot be cured currently, while the pursuit of a functional cure seems to be an accessible goal, in which the condition mainly depends on the serum hepatitis B surface antigen (HBsAg) levels. HBsAg may be downregulated by protein ubiquitination, which may facilitate finding a new potential intervention target for functional cure of CHB. We confirmed that β-transducin repeat-containing protein (β-TrCP) was the E3 ubiquitin ligase of HBsAg. β-TrCP specifically downregulated the expression of Myc-HBsAg. The degradation of Myc-HBsAg occurred via the proteasome pathway. Knockdown of β-TrCP increased Myc-HBsAg levels in HepG2 cells. The study further indicated that β-TrCP could affect the K48-linked polyubiquitin chain by acting on Myc-HBsAg.

Characterization of integrated hepatitis B virus DNA harboring pre‐S mutations in hepatocellular carcinoma patients with ground glass hepatocytes

“…It has been reported that mTOR represses the HBsAg transcription in HCC 40 . E3 ubiquitin ligase β‐TrCP could induce polyubiquitination of HBsAg and result in its ubiquitination degradation 41 . Therefore, different mechanisms may involve in the HBsAg expression or accumulation.…”

“…40 E3 ubiquitin ligase β-TrCP could induce polyubiquitination of HBsAg and result in its ubiquitination degradation 41. Therefore, different mechanisms may involve in the HBsAg expression or accumulation.Further study is needed to clarify regulatory mechanisms in transcription and translation of HBsAg from iDNA.…”