Association of hepatitis B virus polymerase with promyelocytic leukemia nuclear bodies mediated by the S100 family protein p11.

Abstract

Hepatitis B virus (HBV) polymerase (Pol) interacts with cellular chaperone proteins and thereby performs multiple functions necessary for viral replication. Yeast two-hybrid analysis was applied to identify additional cellular targets required for HBV Pol function. HBV Pol interacted with S100A10 (p11), a Ca(2+)-modulated protein previously shown to bind to annexin II. The interaction between HBV Pol and p11 was confirmed by co-immunoprecipitation of the two proteins synthesized either in vitro or in transfected cells and by inhibition of the DNA polymerase activity of HBV Pol by p11. Immunofluorescence analysis of transfected human cell lines revealed that, although most HBV Pol and p11 was restricted to the cytoplasm, a small proportion of each protein colocalized as nuclear speckles; HBV Pol was not detected in the nucleus in the absence of p11. The HBV Pol-p11 nuclear speckles coincided with nuclear bodies containing the promyelocytic leukemia protein PML. Furthermore, the association of HBV Pol-p11 with PML was increased by exposure of cells to EGTA and inhibited by valinomycin. These results suggest a role for p11 in modulation of HBV Pol function and implicate PML nuclear bodies and intracellular Ca(2+) in viral replication.

• Authors: Juhyun Choi, Jin-Sook Chang, Min-Sup Song, Byung-Yoon Ahn, Young Park, Dae-Sik Lim, Ye Sun Han
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 305 Issue 4 Pg. 1049-56 (Jun 13 2003) ISSN: 0006-291X [Print] United States
• PMID: 12767936 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Annexin A2
• Calcium-Binding Proteins
• Chelating Agents
• Gene Products, pol
• Neoplasm Proteins
• Nuclear Proteins
• P protein, Hepatitis B virus
• Promyelocytic Leukemia Protein
• S100 Proteins
• S100 calcium binding protein A10
• Transcription Factors
• Tumor Suppressor Proteins
• PML protein, human
• Egtazic Acid
• Calcium

Topics

• Annexin A2
• Calcium (physiology)
• Calcium-Binding Proteins (analysis, metabolism)
• Cell Nucleus (chemistry, ultrastructure)
• Chelating Agents (pharmacology)
• Cytoplasm (chemistry)
• Egtazic Acid (pharmacology)
• Gene Products, pol (analysis, metabolism)
• Humans
• Microscopy, Fluorescence
• Neoplasm Proteins (analysis)
• Nuclear Proteins
• Promyelocytic Leukemia Protein
• S100 Proteins
• Transcription Factors (analysis)
• Tumor Cells, Cultured
• Tumor Suppressor Proteins
• Two-Hybrid System Techniques