상세 정보

underline
Metadata Downloads : dc(xml) or Excel
Cited 0 time in scopus ci

Title 

Hepatitis B virus X protein enhances transcriptional activity of hypoxia-inducible factor-1α through activation of mitogen-activated protein kinase pathway

Authors 

Y G YooS H OhE S ParkH S ChoN R LeeH S ParkD K KimDae Yeul YuJ K SeongM O Lee

Publisher 

American Society for Biochemistry and Molecular Biology

Issue Date 

2003

Citation 

Journal of Biological Chemistry, vol. 278, no. 40, pp. 39076-39084

Keywords 

proteinsviruses2 (2 amino 3 methoxyphenyl)chromoneangiogenic factorcobalt chloridecyclic AMP responsive element binding protein binding proteinhepatitis b virus x proteinhypoxia inducible factor 1alphamitogen activated protein kinasemitogen activated protein kinase inhibitor

Abstract 

Hepatitis B virus X protein (HBx) of the hepatitis B virus was strongly implicated in angiogenesis and metastasis during hepatocarcinogenesis. Here, we explored the possibility of cross-talk between HBx and hypoxia-inducible factor-1α (HIF-1α), a potent transcriptional inducer of angiogenic factors. First, we showed that stability of HIF-1α protein was increased by HBx in HBx-inducible Chang liver cells as well as in transient HBx expression system of non-hepatic cells. Immunofluorescence studies revealed that the HBx-induced HIF-1α was partially translocated into the nucleus in majority of cells while additional CoCl2-induced hypoxic condition caused complete nuclear translocation. Second, HBx induced both phosphorylation of HIF-1α and activation of p42/p44 mitogen-activated protein kinases (MAPKs), which were synergistically enhanced in the presence of CoCl2. Furthermore, HBx enhanced transcriptional activity of HIF-1αa in the reporter genes encoding hypoxia response element or VEGF promoter. Either treatment of MEK inhibitor PD98059 or coexpression of dominant-negative MAPK mutants abolished the HBx-induced transcriptional activity and protein stability as well as nuclear translocation of HIF-1α, suggesting that HBx activates HIF-1α through MAPK pathway. Third, the association of HIF-1α with von Hippel-Lindau was decreased but the association with CREB-binding protein was enhanced in the presence of HBx, suggesting the molecular mechanism by which HBx enhances the protein stability and transactivation function of HIF-1α. Finally, we demonstrated that expression of HIF-1α and vascular endothelial growth factor was increased in the liver of HBx-transgenic mice, suggesting that the cross-talk between HIF-1α and HBx may lead to transcriptional activation of HIF-1α target genes, which play a critical role in hepatocarcinogenesis.

ISSN 

0021-9258

Link 

http://dx.doi.org/10.1074/jbc.M305101200

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


There are no files associated with this item.
qrcode

FusionCharts.
DSpace Software Coptright(c) 2010 MIT and Hewleft-Packard  /  KRIBB-REPOSITORY ( Email:jakim@kribb.re.kr)