Hepatitis B Virus X Protein Inhibits Transforming Growth Factor-beta-induced Apoptosis through the Activation of Phosphatidylinositol 3-Kinase Pathway

in Sciences Citation Index(SCI), 科學引文索引資料庫(SCI)
標題Hepatitis B Virus X Protein Inhibits Transforming Growth Factor-beta-induced Apoptosis through the Activation of Phosphatidylinositol 3-Kinase Pathway
出版類型SCI(Sciences Citation Index)
出版年度2000
AuthorsWen-Ling Shih, 施玟玲
開始頁25858
頁數6
出版日期2000 / 8
其他編號0000
中文摘要

Transforming growth factor-b (TGF-b) is a potent inducer
of apoptosis in Hep 3B cells. This work investigated
how hepatitis B virus X protein (HBx) affects TGFb-
induced apoptosis. Trypan blue exclusion and colony
formation assays revealed that HBx increased the ID50
toward TGF-b. In the presence of HBx, TGF-b-induced
DNA laddering was decreased, indicating that HBx had
the ability to block TGF-b-induced apoptosis. Furthermore,
HBx did not alter the expression levels of type I
and type II TGF-b receptors. HBx did not affect TGF-binduced
activation of promoter activities of the plasminogen
activator inhibitor-1 (PAI-1) gene. These results
indicate that HBx interferes with only a subset of TGF-b
activity. In the presence of phosphatidylinositol (PI)
3-kinase inhibitors, wortmannin or LY294002, the HBxmediated
inhibitory effect on TGF-b-induced apoptosis
was alleviated. In addition, the tyrosine phosphorylation
levels of the regulatory subunit p85 of phosphatidylinositol
3-kinase (PI 3-kinase) and PI 3-kinase activity
were elevated in stable clones with HBx expression.
Transactivation-deficient mutants of HBx lost their ability
to inhibit TGF-b-induced apoptosis. Phosphorylation
of the p85 subunit of PI 3-kinase and Akt, a downstream
target of PI 3-kinase, was not observed in stable clones
with transactivation-deficient HBx mutant’s expression.
Thus, the anti-apoptotic effect of HBx against TGF-b can
be mediated through the activation of the PI 3-kinase
signaling pathway, and the transactivation function of
HBx is required for its anti-apoptosis activity.

期刊名稱The Journal of Biological Chemistry
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