The bovine papillomavirus type 4 E8 protein binds to ductin and causes loss of gap junctional intercellular communication in primary fibroblasts

The E8 open reading frame of bovine papillomavirus type 4 encodes a small hydrophobic polypeptide which contributes to cell transformation by conferring anchorage-independent growth. Using an in vitro translation system, we show that the E8 polypeptide binds to ductin, the 16-kDa proteolipid that forms transmembrane channels in both gap junctions and vacuolar H+-ATPase. This association is not due to nonspecific hydrophobic interactions. PPA1, a Saccharomyces cerevisiae polypeptide homologous (with 25% identity) to ductin, does not complex with E8. Furthermore, E5B, structurally similar to E8 but with no transforming activity, does not form a complex with ductin. Primary bovine fibroblasts expressing E8 show a loss of gap junctional intercellular communication, and it is suggested that this results from the interaction between E8 and ductin.

[1]  M. Finbow,et al.  Membrane insertion and assembly of ductin: a polytopic channel with dual orientations. , 1995, The EMBO journal.

[2]  J. Kartenbeck,et al.  Human papillomavirus type 16 E5 protein affects cell-cell communication in an epithelial cell line , 1995, Journal of virology.

[3]  D. McCance,et al.  The E5 oncoprotein of human papillomavirus type 16 inhibits the acidification of endosomes in human keratinocytes , 1995, Journal of virology.

[4]  M. Campo,et al.  Experimental reproduction of the papilloma-carcinoma complex of the alimentary canal in cattle. , 1994, Carcinogenesis.

[5]  R. Schlegel,et al.  The human T-cell leukemia/lymphotropic virus type I p12I protein cooperates with the E5 oncoprotein of bovine papillomavirus in cell transformation and binds the 16-kilodalton subunit of the vacuolar H+ ATPase , 1993, Journal of virology.

[6]  R. Schlegel,et al.  The human papillomavirus type 6 and 16 E5 proteins are membrane-associated proteins which associate with the 16-kilodalton pore-forming protein , 1993, Journal of virology.

[7]  M. Finbow,et al.  Is the gap junction channel--the connexon--made of connexin or ductin? , 1993, Journal of cell science.

[8]  D. Apps,et al.  Disposition and orientation of ductin (DCCD-reactive vacuolar H(+)-ATPase subunit) in mammalian membrane complexes. , 1993, Experimental cell research.

[9]  D. McCance,et al.  The E5 oncoprotein of human papillomavirus type 16 transforms fibroblasts and effects the downregulation of the epidermal growth factor receptor in keratinocytes , 1993, Journal of virology.

[10]  J. Settleman,et al.  Genetic definition of a new bovine papillomavirus type 1 open reading frame, E5B, that encodes a hydrophobic protein involved in altering host-cell protein processing , 1993, Journal of virology.

[11]  W. Pennie,et al.  Analysis of the transforming functions of bovine papillomavirus type 4. , 1993, Virology.

[12]  A. Balmain,et al.  Cell‐cell communication and growth control of normal and cancer cells: Evidence and hypothesis , 1993 .

[13]  N. Nelson.  Organellar proton-ATPases , 1992, Current Biology.

[14]  G. Carpenter,et al.  Analysis of the influences of the E5 transforming protein on kinetic parameters of epidermal growth factor binding and metabolism , 1992, Journal of cellular physiology.

[15]  D. Verma,et al.  Topology and phosphorylation of soybean nodulin-26, an intrinsic protein of the peribacteroid membrane , 1992, The Journal of cell biology.

[16]  E. Eliopoulos,et al.  Structure of a 16 kDa integral membrane protein that has identity to the putative proton channel of the vacuolar H(+)-ATPase. , 1992, Protein engineering.

[17]  R. Schlegel,et al.  The E5 oncoprotein target: A 16‐kDa channel‐forming protein with diverse functions , 1991, Molecular carcinogenesis.

[18]  W. Pennie,et al.  Cooperation between bovine papillomavirus type 4 and ras in the morphological transformation of primary bovine fibroblasts. , 1990, The Journal of general virology.

[19]  M. Finbow,et al.  The gap junction-like form of a vacuolar proton channel component appears not to be an artifact of isolation: an immunocytochemical localization study. , 1990, Experimental cell research.

[20]  R. Jensen,et al.  A yeast protein, homologous to the proteolipid of the chromaffin granule proton-ATPase, is important for cell growth. , 1990, Biochemical and biophysical research communications.

[21]  R. Schlegel,et al.  The E5 oncoprotein of bovine papillomavirus binds to a 16 kd cellular protein. , 1990, The EMBO journal.

[22]  D. Lowy,et al.  The bovine papillomavirus E5 transforming protein can stimulate the transforming activity of EGF and CSF-1 receptors , 1989, Cell.

[23]  M. Willingham,et al.  The E5 oncoprotein of bovine papillomavirus is oriented asymmetrically in Golgi and plasma membranes. , 1989, Virology.

[24]  F. Serras,et al.  Inhibition of dye-coupling in Patella (Mollusca) embryos by microinjection of antiserum against nephrops (Arthropoda) gap junctions. , 1988, Experimental cell research.

[25]  M. Mandel,et al.  cDNA sequence encoding the 16-kDa proteolipid of chromaffin granules implies gene duplication in the evolution of H+-ATPases. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[26]  E. Kam,et al.  Communication compartments in mixed cell cultures. , 1985, Experimental cell research.

[27]  M. Campo,et al.  Molecular Cloning of Bovine Papillomavirus Genomes and Comparison of Their Sequence Homologies by Heteroduplex Mapping , 1982 .

[28]  Peter H. Seeburg,et al.  The primary structure and genetic organization of the bovine papillomavirus type 1 genome , 1982, Nature.

[29]  I. Selman,et al.  High incidence area of cattle cancer with a possible interaction between an environmental carcinogen and a papilloma virus , 1978, Nature.