Proteolytic conversion of hepatitis B virus e antigen precursor to end product occurs in a postendoplasmic reticulum compartment

At least two proteolytic events are involved in the biogenesis of hepatitis B virus e antigen. The first proteolytic event removes the signal peptide and results in the translocation of the precursor protein, P22, into the lumen of the endoplasmic reticulum (ER). The second proteolytic event removes the carboxy-terminal arginine-rich sequence of P22 and converts it to the 16-kDa hepatitis B virus e antigen end product. In contrast to the first proteolytic event, the second proteolytic event is suppressed by brefeldin A, a chemical that inhibits the transport of protein from the ER to the Golgi apparatus. In subcellular fractionation experiments, P22 was detected in both the ER and the Golgi fractions, but P16 was detected only in the Golgi fraction. On the basis of these results, we conclude that the conversion of P22 to P16 occurs ina post-ER compartment, mostly likely the Golgi apparatus.

[1]  J. Ou,et al.  Phosphorylation of hepatitis B virus precore and core proteins , 1991, Journal of virology.

[2]  J. Rothman,et al.  A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein β-adaptin , 1991, Nature.

[3]  J. Ou,et al.  Transport of hepatitis B virus precore protein into the nucleus after cleavage of its signal peptide , 1989, Journal of virology.

[4]  A. S. Lee,et al.  The rat 78,000 dalton glucose-regulated protein (GRP78) as a precursor for the rat steroidogenesis-activator polypeptide (SAP): the SAP coding sequence is homologous with the terminal end of GRP78. , 1989, Molecular endocrinology.

[5]  T. Nakaki,et al.  Enhanced transcription of the 78,000-dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1) , 1989, Molecular and cellular biology.

[6]  J. Lippincott-Schwartz,et al.  Rapid redistribution of Golgi proteins into the ER in cells treated with brefeldin A: Evidence for membrane cycling from Golgi to ER , 1989, Cell.

[7]  H. Blum,et al.  The molecular biology of hepatitis B virus. , 1989, Trends in genetics : TIG.

[8]  W. Rutter,et al.  A signal peptide encoded within the precore region of hepatitis B virus directs the secretion of a heterogeneous population of e antigens in Xenopus oocytes. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[9]  L. Hendershot,et al.  Identity of the immunoglobulin heavy-chain-binding protein with the 78,000-dalton glucose-regulated protein and the role of posttranslational modifications in its binding function , 1988, Molecular and cellular biology.

[10]  W. Gerlich,et al.  Formation of transmembraneous hepatitis B e-antigen by cotranslational in vitro processing of the viral precore protein. , 1988, Virology.

[11]  W. Rutter,et al.  Targeting of the hepatitis B virus precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm , 1988, The Journal of cell biology.

[12]  P. Galle,et al.  Expression and replication of the hepatitis B virus genome under foreign promoter control. , 1987, Nucleic acids research.

[13]  H. Will,et al.  Expression of the hepatitis B virus core gene in vitro and in vivo , 1987, Journal of virology.

[14]  H. Varmus,et al.  The molecular biology of the hepatitis B viruses. , 1987, Annual review of biochemistry.

[15]  Y. Misumi,et al.  Novel blockade by brefeldin A of intracellular transport of secretory proteins in cultured rat hepatocytes. , 1986, The Journal of biological chemistry.

[16]  A. Siddiqui,et al.  Expression of hepatitis B viral core region in mammalian cells , 1986, Molecular and cellular biology.

[17]  J. Kearney,et al.  Posttranslational association of immunoglobulin heavy chain binding protein with nascent heavy chains in nonsecreting and secreting hybridomas , 1986, The Journal of cell biology.

[18]  W. Rutter,et al.  Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[19]  R. Kelly Pathways of protein secretion in eukaryotes. , 1985, Science.

[20]  P. Vassalli,et al.  Lectin-binding sites as markers of Golgi subcompartments: proximal-to- distal maturation of oligosaccharides , 1983, The Journal of cell biology.

[21]  P Berg,et al.  Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. , 1982, Journal of molecular and applied genetics.

[22]  F. Tsuda,et al.  Association of dane particles with e antigen in the serum of asymptomatic carriers of hepatitis B surface antigen. , 1976, Journal of immunology.

[23]  J. Nielsen,et al.  Incidence and meaning of the "e" determinant among hepatitis-B-antigen positive patients with acute and chronic liver diseases. Report from the Copenhagen Hepatitis Acuta Programme. , 1974, Lancet.