Hepatitis B virus X protein regulates transactivation activity and protein stability of the cancer-amplified transcription coactivator ASC-2.
Hepatitis B virus X protein (HBx) is a transcriptional coactivator that plays a significant role in the regulation of genes involved in inflammation and cell survival. A recently identified cellular coactivator, activating signal cointegrator 2 (ASC-2), is enriched in liver cancer cells and associates with many transcription factors that are active in hepatocytes. The tissue colocalization of these 2 proteins, in view of their similar regulatory functions, led us to examine whether HBx and ASC-2 cooperate in transcriptional activation of gene expression. Glutathione S-transferase (GST) pull-down assays and mammalian 2-hybrid analysis show that the transactivation domain of HBx interacts with the C-terminal domain of ASC-2. In fact, these 2 proteins associated in a ternary complex that included the transcriptional activator retinoid X receptor (RXR). Mechanistically, on expression of HBx, the half-life of the ASC-2 coactivator is observed to increase in concordance with the observed increase in ASC-2-dependent coactivation of transcription. In conclusion, these results show that HBx stabilizes the cellular coactivator ASC-2 through direct protein-protein interaction, affecting the regulation of genes actively transcribed in liver cancer cells.
Department of Molecular Biology, Pusan National University, Busan, Korea.
Hee Jeong
HJ
Kong
Min Jung
MJ
Park
SunHwa
S
Hong
Hyun Jung
HJ
Yu
Young Chul
YC
Lee
Young Hyun
YH
Choi
JaeHun
J
Cheong
D045744:Cell Line, Tumor; D004347:Drug Interactions; D004355:Drug Stability; D004357:Drug Synergism; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D056918:Nuclear Receptor Coactivators; D017434:Protein Structure, Tertiary / Q000502:physiology; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D015534:Trans-Activators / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D047908:Intracellular Signaling Peptides and Proteins; C486559:NCOA6 protein, human; D056918:Nuclear Receptor Coactivators; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein