Id-1 Induces Proteasome-dependent Degradation of the HBX Protein

Ming Tat Ling, Yung Tuen Chiu, Kin Wah Lee, Steve Chin Lung Leung, Maggie Ka Lai Fung, Xianghong Wang, Kwong Fai Wong, Yong Chuan Wong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

22 Citations (Scopus)

Abstract

Id-1 is a member of the HLH protein family that regulates a wide range of cellular processes such as cell proliferation, apoptosis, senescence and overexpression of Id-1 was recently suggested to play roles in the development and progression of different cancers. Previously, Id-1 was shown to physically interact with the viral protein E1A. Meanwhile, Id-1 expression was found to be regulated by several of the virus-encoded proteins, suggesting that Id-1 may be a common cellular target of the viral proteins. Here, we report that Id-1 interacts with the Hepatitis-B virus (HBV)-encoded protein HBX and regulates its stability in hepatocellular carcinoma (HCC) cells. We found that in HCC cells, ectopic Id-1 expression significantly decreased the half-life of the HBX protein, indicating that HBX is destabilized by Id-1. Meanwhile, the Id-1-induced HBX degradation was found to be inhibited by treatment with proteasome inhibitor, suggesting that this process is mediated through the proteasome pathway. Interestingly, while Id-1 did not induce HBX-ubiquitination, we found that removal of all the lysine residues of the HBX protein protects it from the effect of Id-1, indicating that ubiquitination is still required for the Id-1-mediated HBX degradation. Meanwhile, we found that Id-1 binds to the proteasome subunit C8 and facilitates its interaction with the HBX protein and disruption of this interaction completely abolishes the negative effect of Id-1 on HBX protein stability. Taken together, our results demonstrated a novel function of Id-1 in regulating HBX protein stability through interaction with the proteasome.
Original languageEnglish
Pages (from-to)34-43
Number of pages10
JournalJournal of Molecular Biology
Volume382
Issue number1
DOIs
Publication statusPublished - 26 Sep 2008
Externally publishedYes

Keywords

  • C8
  • degradation
  • HBX
  • Id-1
  • proteasome

ASJC Scopus subject areas

  • Virology

Cite this