The carboxy-terminus of the hepatitis B virus X protein is necessary and sufficient for the activation of hypoxia-inducible factor-1alpha.
Hepatitis B virus X protein (HBx) of the hepatitis B virus is strongly implicated in angiogenesis and metastasis during hepatocarcinogenesis. Previously, we reported that HBx enhances activity of hypoxia-inducible factor-1alpha (HIF-1alpha), a potent transactivator that induces angiogenic factors. Here, we delineate the structural region of HBx that potentiates HIF-1alpha. The carboxy-terminus of HBx increased the stability of HIF-1alpha protein, probably through inhibiting interaction with von Hippel-Lindau protein. Further, the carboxy-terminus of HBx enhanced the transactivation function of HIF-1alpha by enhancing its association with CREB binding protein (CBP). Finally, we demonstrated the physical association of HBx with the basic helix-loop-helix/PER-ARNT-SIM domain, the inhibitory domain, and the carboxy-terminal transactivation domain of HIF-1alpha in vivo.
Yoo
Young-Gun
YG
Department of Bioscience and Biotechnology, Sejong University, Seoul 140-747, Republic of Korea.
Cho
Sayeon
S
Park
Sun
S
Lee
Mi-Ock
MO
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D011485:Protein Binding; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein