Natural variants of hepatitis B virus X protein have differential effects on the expression of cyclin-dependent kinase inhibitor p21 gene

Hyun Jin Kwun, Kyung Lib Jang

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Despite the extensive studies on the roles of hepattis B virus X protein (HBx), the effects of HBx on the important cellular processes such as cell growth, cell transformation and apoptosis remain controversial. Our previous study showed that the balance between p53-dependent activation and p53-independent repression by HBx determines the expression level of cyclin-dependent kinase inhibitor p21. In the present study, we further demonstrate that HBx natural variants have differential effects on p21 expression. The critical sites in HBx were identified as residues Ser-101 for activation and Met-130 for repression, respectively. The HBx variants with Ser-101 instead of Pro-101 stabilized p53 more efficiently, probably by protecting it from the MDM2-medlated degradation. On the other hand, the Met-130-containing HBx strongly repressed p21 expression by inhibiting Sp1 activity. Overall, the effect of HBx on p21 expression seems to be determined by the balance between the opposite activities. Depending on their potentials to regulate p21 expression, HBx variants showed different effects on the cell cycle progression, and eventually on the cell growth rate, implicating its biological significance. The present study may provide a clue to explaining the contradictory results related to cell growth regulation by HBx as well as to understanding the progression of hepatic diseases in HBV-positive patients.

Original languageEnglish (US)
Pages (from-to)2202-2213
Number of pages12
JournalNucleic acids research
Volume32
Issue number7
DOIs
StatePublished - Jul 14 2004

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Cyclin-Dependent Kinase Inhibitor p21
Genes
Growth
Cercopithecine Herpesvirus 1
Disease Progression
Cell Cycle
Apoptosis
hepatitis B virus X protein
Liver
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

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abstract = "Despite the extensive studies on the roles of hepattis B virus X protein (HBx), the effects of HBx on the important cellular processes such as cell growth, cell transformation and apoptosis remain controversial. Our previous study showed that the balance between p53-dependent activation and p53-independent repression by HBx determines the expression level of cyclin-dependent kinase inhibitor p21. In the present study, we further demonstrate that HBx natural variants have differential effects on p21 expression. The critical sites in HBx were identified as residues Ser-101 for activation and Met-130 for repression, respectively. The HBx variants with Ser-101 instead of Pro-101 stabilized p53 more efficiently, probably by protecting it from the MDM2-medlated degradation. On the other hand, the Met-130-containing HBx strongly repressed p21 expression by inhibiting Sp1 activity. Overall, the effect of HBx on p21 expression seems to be determined by the balance between the opposite activities. Depending on their potentials to regulate p21 expression, HBx variants showed different effects on the cell cycle progression, and eventually on the cell growth rate, implicating its biological significance. The present study may provide a clue to explaining the contradictory results related to cell growth regulation by HBx as well as to understanding the progression of hepatic diseases in HBV-positive patients.",
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Natural variants of hepatitis B virus X protein have differential effects on the expression of cyclin-dependent kinase inhibitor p21 gene. / Kwun, Hyun Jin; Jang, Kyung Lib.

In: Nucleic acids research, Vol. 32, No. 7, 14.07.2004, p. 2202-2213.

Research output: Contribution to journalArticle

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