Binding of bovine papillomavirus type 4 E8 to ductin (16K proteolipid), down-regulation of gap junction intercellular communication and full cell transformation are independent events.

The E8 open reading frame of bovine papillomavirus type 4 encodes a small hydrophobic polypeptide that contributes to primary cell transformation by conferring to cells the ability to form foci and to grow in low serum and in suspension. Wild-type E8 binds in vitro to ductin, a component of gap junctions, and this binding is accompanied by a loss of gap junction intercellular communication in transformed bovine fibroblasts. However, through the analysis of a panel of E8 mutants, we show here that binding of E8 to ductin is not sufficient for down-regulation of gap junction communication and that there is no absolute correlation between down-regulation of gap junction communication and the transformed phenotype.

[1]  G. Grindlay,et al.  A mutational analysis of the transforming functions of the E8 protein of bovine papillomavirus type 4. , 1999, Virology.

[2]  D. Goodenough,et al.  Diverse functions of vertebrate gap junctions. , 1998, Trends in cell biology.

[3]  M. Campo,et al.  BPV-4 E8 transforms NIH3T3 cells, up-regulates cyclin A and cyclin A-associated kinase activity and de-regulates expression of the cdk inhibitor p27Kip1 , 1998, Oncogene.

[4]  L. Scobie,et al.  Viral proteins of bovine papillomavirus type 4 during the development of alimentary canal tumours. , 1997, Veterinary journal.

[5]  M. Finbow,et al.  The vacuolar H+-ATPase: a universal proton pump of eukaryotes. , 1997, The Biochemical journal.

[6]  M. Campo,et al.  The bovine papillomavirus type 4 E8 protein binds to ductin and causes loss of gap junctional intercellular communication in primary fibroblasts , 1996, Journal of virology.

[7]  R. Schlegel,et al.  E5 oncoprotein transmembrane mutants dissociate fibroblast transforming activity from 16-kilodalton protein binding and platelet-derived growth factor receptor binding and phosphorylation , 1996, Journal of virology.

[8]  T. Slaga,et al.  The expression of gap junctional proteins during different stages of mouse skin carcinogenesis. , 1995, Carcinogenesis.

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

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

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

[12]  M. Finbow,et al.  Ductin – a proton pump component, a gap junction channel and a neurotransmitter release channel , 1995, BioEssays : news and reviews in molecular, cellular and developmental biology.

[13]  R. Schlegel,et al.  Mutation of the bovine papillomavirus E5 oncoprotein at amino acid 17 generates both high- and low-transforming variants , 1994, Journal of virology.

[14]  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.

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

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

[17]  R. Schlegel,et al.  The BPV‐1 E5 protein, the 16 kDa membrane pore‐forming protein and the PDGF receptor exist in a complex that is dependent on hydrophobic transmembrane interactions. , 1992, EMBO Journal.

[18]  E. Kam,et al.  Communication compartments in hair follicles and their implication in differentiative control. , 1992, Development.

[19]  D. DiMaio,et al.  The central hydrophobic domain of the bovine papillomavirus E5 transforming protein can be functionally replaced by many hydrophobic amino acid sequences containing a glutamine , 1992, Journal of virology.

[20]  T. Andrésson,et al.  Bovine papillomavirus E5 oncoprotein binds to the 16K component of vacuolar H+-ATPases , 1991, Nature.

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

[22]  D. DiMaio,et al.  44-amino-acid E5 transforming protein of bovine papillomavirus requires a hydrophobic core and specific carboxyl-terminal amino acids , 1988, Molecular and cellular biology.

[23]  E. Kam,et al.  Effects of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate on junctional communication in intact mouse skin: persistence of homologous communication and increase of epidermal-dermal coupling. , 1988, Carcinogenesis.