http://www.cnr.it/ontology/cnr/individuo/prodotto/ID11746
Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity (Articolo in rivista)
- Type
- Label
- Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity (Articolo in rivista) (literal)
- Anno
- 2009-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1186/1756-9966-28-4 (literal)
- Alternative label
Di Domenico, F; Foppoli, C; Blarzino, C; Perluigi, M; Paolini, F; Morici, S; Coccia, R; Cini, C; De Marco, F (2009)
Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity
in Journal of experimental & clinical cancer research (Online)
(literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Di Domenico, F; Foppoli, C; Blarzino, C; Perluigi, M; Paolini, F; Morici, S; Coccia, R; Cini, C; De Marco, F (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
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- Note
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Dipartimento di Scienze Biochimiche, Università di Roma \"La Sapienza\";
Istituto di Biologia e Patologia Molecolari, CNR;
Istituto \"Regina Elena\" per la Ricerca sul Cancro (literal)
- Titolo
- Expression of human papilloma virus type 16 E5 protein in amelanotic melanoma cells regulates endo-cellular pH and restores tyrosinase activity (literal)
- Abstract
- Background: Melanin synthesis, the elective trait of melanocytes, is regulated by tyrosinase activity. In tyrosinasepositive
amelanotic melanomas this rate limiting enzyme is inactive because of acidic endo-melanosomal pH. The E5
oncogene of the Human Papillomavirus Type 16 is a small transmembrane protein with a weak transforming activity and
a role during the early steps of viral infections. E5 has been shown to interact with 16 kDa subunit C of the transmembrane
Vacuolar ATPase proton pump ultimately resulting in its functional suppressions. However, the cellular effects
of such an interaction are still under debate. With this work we intended to explore whether the HPV16 E5 oncoprotein
does indeed interact with the vacuolar ATPase proton pump once expressed in intact human cells and whether this
interaction has functional consequences on cell metabolism and phenotype.
Methods: The expression of the HPV16-E5 oncoproteins was induced in two Tyrosinase-positive amelanotic
melanomas (the cell lines FRM and M14) by a retroviral expression construct. Modulation of the intracellular pH was
measured with Acridine orange and fluorescence microscopy. Expression of tyrosinase and its activity was followed by
RT-PCR, Western Blot and enzyme assay. The anchorage-independence growth and the metabolic activity of E5
expressing cells were also monitored.
Results: We provide evidence that in the E5 expressing cells interaction between E5 and V-ATPase determines an
increase of endo-cellular pH. The cellular alkalinisation in turn leads to the post-translational activation of tyrosinase,
melanin synthesis and phenotype modulation. These effects are associated with an increased activation of tyrosine
analogue anti-blastic drugs.
Conclusion: Once expressed within intact human cells the HPV16-E5 oncoprotein does actually interact with the
vacuolar V-ATPase proton pump and this interaction induces a number of functional effects. In amelanotic melanomas
these effects can modulate the cell phenotype and can induce a higher sensitivity to tyrosine related anti-blastic drugs. (literal)
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