The HPV-16 E5 oncogene and bafilomycin A(1) influence cell motility.
It is known that the proper function of the vacuolar H(+)-ATPase is inhibited by bafilomycin A(1). In transfected cells the E5 protein interacts with the 16 kDa subunit of the vacuolar H(+)-ATPase. Thereby the pH gradient in endocytic structures is impaired. The present study demonstrates for the first time that the inhibition of the vacuolar H(+)-ATPase in NIH3T3 cells with bafilomycin A(1) or by transfection of cells with the HPV-16 E5 oncogene leads to a changed morphology and a reduced motility as shown by computer-assisted video recordings and image analysis. Bafilomycin A(1) potentiates the effect of the E5 protein on cell motility and this cooperative effect indicates that the E5 protein and bafilomycin A(1) either target the vacuolar H(+)-ATPase differently or that the E5 protein has additional targets in transfected cells. Our data therefore show that proper function of the vacuolar H(+)-ATPase is needed for normal cell locomotion.
Thomsen
P
P
The Protein Laboratory, Institute of Molecular Pathology, University of Copenhagen, Panum Institute, Bldg. 6.2, Blegdamsvej 3C, DK-2200, Copenhagen N, Denmark.
Rudenko
O
O
Berezin
V
V
Norrild
B
B
D016475:3T3 Cells; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects; D004357:Drug Synergism; D015870:Gene Expression; D018942:Macrolides; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000494:pharmacology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000086082:Viroporin Proteins
D000900:Anti-Bacterial Agents; D018942:Macrolides; D009856:Oncogene Proteins, Viral; D006180:Proton-Translocating ATPases; C054859:oncogene protein E5, Human papillomavirus type 16; D000086082:Viroporin Proteins; C040929:bafilomycin A1