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[[Image:HBV genome.png|right|thumb|300px|The genome organisation of HBV. The genes overlap. (ORF X, in yellow, encodes HBx)]]
[[Image:HBV genome.png|right|thumb|300px|The genome organisation of HBV. The genes overlap. (ORF X, in yellow, encodes HBx)]]

'''HBx''' is a [[hepatitis B]] [[viral protein]].<ref name="pmid17699583">{{cite journal |author=McClain SL, Clippinger AJ, Lizzano R, Bouchard MJ |title=Hepatitis B virus replication is associated with an HBx-dependent mitochondrion-regulated increase in cytosolic calcium levels |journal=J. Virol. |volume=81 |issue=21 |pages=12061–5 |year=2007 |month=November |pmid=17699583 |pmc=2168786 |doi=10.1128/JVI.00740-07 |url=http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=17699583}}</ref><ref name="pmid12829810">{{cite journal |author=Bouchard MJ, Puro RJ, Wang L, Schneider RJ |title=Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication |journal=J. Virol. |volume=77 |issue=14 |pages=7713–9 |year=2003 |month=July |pmid=12829810 |pmc=161925 |doi= 10.1128/JVI.77.14.7713-7719.2003|url=http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=12829810}}</ref>
'''HBx''' is a [[hepatitis B]] [[viral protein]].<ref name="pmid17699583">{{cite journal |author=McClain SL, Clippinger AJ, Lizzano R, Bouchard MJ |title=Hepatitis B virus replication is associated with an HBx-dependent mitochondrion-regulated increase in cytosolic calcium levels |journal=J. Virol. |volume=81 |issue=21 |pages=12061–5 |year=2007 |month=November |pmid=17699583 |pmc=2168786 |doi=10.1128/JVI.00740-07 |url=http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=17699583}}</ref><ref name="pmid12829810">{{cite journal |author=Bouchard MJ, Puro RJ, Wang L, Schneider RJ |title=Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication |journal=J. Virol. |volume=77 |issue=14 |pages=7713–9 |year=2003 |month=July |pmid=12829810 |pmc=161925 |doi= 10.1128/JVI.77.14.7713-7719.2003|url=http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=12829810}}</ref>


The protein is 154 [[amino acid]]s long and interferes with transcription, signal transduction, [[cell cycle]] progress, protein degradation, [[apoptosis]] and chromosomal stability in the host. It forms a heterodimeric complex formation with its cellular target protein ([[HBX interacting protein]]: HBXIP) which triggering deregulation of [[centrosome]] dynamics and [[mitotic spindle]] formation.<ref>Wen Y, Golubkov VS, Strongin AY, Jiang W, Reed JC (2008) Interaction of hepatitis B viral oncoprotein with cellular target HBXIP dysregulates centrosome dynamics and mitotic spindle formation. J Biol Chem 283(5):2793-803</ref> It interacts with DDB1 ([[Damaged DNA Binding Protein 1]]) redirecting the [[ubiquitin ligase]] activity of the [[CUL4]]-DDB1 [[Ubiquitin ligase|E3]] complexes, which are intimately involved in the intracellular regulation of [[DNA]] replication and repair, [[transcription (genetics)|transcription]] and signal transduction.<ref>Li T, Robert EI, van Breugel PC, Strubin M, Zheng N (2010) A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery.
The protein is 154 [[amino acid]]s long and interferes with transcription, signal transduction, [[cell cycle]] progress, protein degradation, [[apoptosis]] and chromosomal stability in the host. It forms a heterodimeric complex formation with its cellular target protein ([[HBX interacting protein]]: HBXIP) which triggering deregulation of [[centrosome]] dynamics and [[mitotic spindle]] formation.<ref>{{cite journal|last1=Wen|first1=Y.|last2=Golubkov|first2=VS. |last3=Strongin|first3=AY.|last4=Jiang|first4=W|last5=Reed|first5=J.C.|year=2008|title=Interaction of hepatitis B viral oncoprotein with cellular target HBXIP dysregulates centrosome dynamics and mitotic spindle formation|journal=Journal of Biological Chemistry|volume=283|issue=5|pages=2793-2803|doi=10.1074/jbc.M708419200|pmid=18032378|url=http://www.jbc.org/content/283/5/2793}}</ref> It interacts with DDB1 ([[Damaged DNA Binding Protein 1]]) redirecting the [[ubiquitin ligase]] activity of the [[CUL4]]-DDB1 [[Ubiquitin ligase|E3]] complexes, which are intimately involved in the intracellular regulation of [[DNA]] replication and repair, [[transcription (genetics)|transcription]] and signal transduction.<ref>{{cite journal|last1=Li|first1=T|last2=Robert|first3=E.I. |last4=van Breugel|first4=P.C.|last5=Strubin|first5=M.|last6=Zheng|first6=N.|year=2010|title=A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery|journal=Nature Structural & Molecular Biology|volume=17|issue=1|pages=105-111|publisher=Nature|doi=10.1038/nsmb.1719|pmc=2823288|pmid=19966799|url=http://www.nature.com/nsmb/journal/v17/n1/full/nsmb.1719.html}}</ref>
Nat Struct Mol Biol 17(1):105-111</ref>


Although Protein X is normally absent in the [[Avihepadnavirus]], a vestigial version has been identified in the duck hepatitis virus genome.<ref name=Lin2000>Lin B, Anderson DA. A vestigial X open reading frame in duck hepatitis B virus. Intervirol. 2000;43:185–190</ref>
Although Protein X is normally absent in the [[Avihepadnavirus]], a vestigial version has been identified in the duck hepatitis virus genome.<ref name=Lin2000>{{cite journal|last1=Lin|first1=B.|last2=Anderson|first3=D.A.|year=2000|title=A vestigial X open reading frame in duck hepatitis B virus|journal=Intervirology|volume=43|issue=3|pages=185-190|publisher=Karger|pmid=11044813|url=http://www.karger.com/Article/PDF/25037}}</ref>


Although it lacks significant homology with any known vertebrate proteins, it seems likely that it evolved from a [[DNA glycosylase]].<ref name=van_Hemert2011>van Hemert FJ, van de Klundert MA, Lukashov VV, Kootstra NA, Berkhout B, Zaaijer HL (2011) Protein x of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase. PLoS One. 2011;6(8):e23392</ref>
Although it lacks significant homology with any known vertebrate proteins, it seems likely that it evolved from a [[DNA glycosylase]].<ref name=van_Hemert2011>{{cite journal|last1=van Hemert|first1=F.J.|last2=van de Klundert|first2=M.A.|last3=Lukashov|first3=V.V.|last4=Kootstra|first4=N.A.|last5=Berkhout |first5=B.|last6=Zaaijer|first=H.L.|year=2011|title=Protein x of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase|journal=PLoS One|volume=6|issue=8|page=e23392|doi=10.1371/journal.pone.0023392|pmid=21850270 |url=http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0023392}}</ref>


Transgenic mice expressing the X protein in liver are more likely than the wild type to develop hepatocellular carcinoma.<ref name=Kew2011>Kew MC (2011) Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma. J Gastroenterol Hepatol 26 Suppl 1:144-52. {{doi|10.1111/j.1440-1746.2010.06546.x}}.</ref>
Transgenic mice expressing the X protein in liver are more likely than the wild type to develop hepatocellular carcinoma.<ref name=Kew2011>{{cite journal|last1=Kew|first1=M.C.|year=2011|title=Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma|journal=Journal of Gastroenterolology and Hepatology|volume=26|issue=Suppl 1|pages=144-152|doi=10.1111/j.1440-1746.2010.06546.x |pmid=21199526|url=http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2010.06546.x/full}}</ref>


==Relation to PRMT1==
==Relation to PRMT1==

Revision as of 08:36, 7 April 2013

The genome organisation of HBV. The genes overlap. (ORF X, in yellow, encodes HBx)

HBx is a hepatitis B viral protein.[1][2]

The protein is 154 amino acids long and interferes with transcription, signal transduction, cell cycle progress, protein degradation, apoptosis and chromosomal stability in the host. It forms a heterodimeric complex formation with its cellular target protein (HBX interacting protein: HBXIP) which triggering deregulation of centrosome dynamics and mitotic spindle formation.[3] It interacts with DDB1 (Damaged DNA Binding Protein 1) redirecting the ubiquitin ligase activity of the CUL4-DDB1 E3 complexes, which are intimately involved in the intracellular regulation of DNA replication and repair, transcription and signal transduction.[4]

Although Protein X is normally absent in the Avihepadnavirus, a vestigial version has been identified in the duck hepatitis virus genome.[5]

Although it lacks significant homology with any known vertebrate proteins, it seems likely that it evolved from a DNA glycosylase.[6]

Transgenic mice expressing the X protein in liver are more likely than the wild type to develop hepatocellular carcinoma.[7]

Relation to PRMT1

In a study purifying cancerous liver cells infected with HBV, the level of expression of protein arginine methyltransferase 1 (PRMT1) was found to be associated with changes in transcription due to the methyltransferase function of PRMT1. Overexpression causes a reduction in the number of HBV genes transcribed, while conversely, underexpression causes an increase. PRMT1 was also found to be recruited by HBV DNA during the replication process to regulate the transcription process. Increased HBx expression in turn leads to an inhibition of PRMT1-mediated protein methylation, benefiting viral replication.[8]

References

  1. ^ McClain SL, Clippinger AJ, Lizzano R, Bouchard MJ (2007). "Hepatitis B virus replication is associated with an HBx-dependent mitochondrion-regulated increase in cytosolic calcium levels". J. Virol. 81 (21): 12061–5. doi:10.1128/JVI.00740-07. PMC 2168786. PMID 17699583. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Bouchard MJ, Puro RJ, Wang L, Schneider RJ (2003). "Activation and inhibition of cellular calcium and tyrosine kinase signaling pathways identify targets of the HBx protein involved in hepatitis B virus replication". J. Virol. 77 (14): 7713–9. doi:10.1128/JVI.77.14.7713-7719.2003. PMC 161925. PMID 12829810. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Wen, Y.; Golubkov, VS.; Strongin, AY.; Jiang, W; Reed, J.C. (2008). "Interaction of hepatitis B viral oncoprotein with cellular target HBXIP dysregulates centrosome dynamics and mitotic spindle formation". Journal of Biological Chemistry. 283 (5): 2793–2803. doi:10.1074/jbc.M708419200. PMID 18032378.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ Li, T; Robert; van Breugel, P.C.; Strubin, M.; Zheng, N. (2010). "A promiscuous alpha-helical motif anchors viral hijackers and substrate receptors to the CUL4-DDB1 ubiquitin ligase machinery". Nature Structural & Molecular Biology. 17 (1). Nature: 105–111. doi:10.1038/nsmb.1719. PMC 2823288. PMID 19966799. {{cite journal}}: |first3= missing |last3= (help)
  5. ^ Lin, B.; Anderson (2000). "A vestigial X open reading frame in duck hepatitis B virus". Intervirology. 43 (3). Karger: 185–190. PMID 11044813. {{cite journal}}: |first3= missing |last3= (help)
  6. ^ van Hemert, H.L.; van de Klundert, M.A.; Lukashov, V.V.; Kootstra, N.A.; Berkhout, B.; Zaaijer (2011). "Protein x of hepatitis B virus: origin and structure similarity with the central domain of DNA glycosylase". PLoS One. 6 (8): e23392. doi:10.1371/journal.pone.0023392. PMID 21850270. {{cite journal}}: More than one of |first1= and |first= specified (help)CS1 maint: unflagged free DOI (link)
  7. ^ Kew, M.C. (2011). "Hepatitis B virus x protein in the pathogenesis of hepatitis B virus-induced hepatocellular carcinoma". Journal of Gastroenterolology and Hepatology. 26 (Suppl 1): 144–152. doi:10.1111/j.1440-1746.2010.06546.x. PMID 21199526.
  8. ^ Benhenda S (2013). "Methyltransferase PRMT1 Is a Binding Partner of HBx and a Negative Regulator of Hepatitis B Virus Transcription". Journal of Virology. 87 (8). American Society for Microbiology: 4360–4371. doi:10.1128/JVI.02574-12. PMID 23388725. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)


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