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.
The human T-cell leukemia/lymphotropic virus type I (HTLV-I) induces T-cell leukemia and transforms human T cells in vitro. A recently identified protein with a molecular weight of 12,000 (12K) (p12I), encoded by single- and double-spliced mRNAs transcribed from the 3' end of the HTLV-I genome, has been shown to localize in the perinuclear compartment and in the cellular endomembranes. The p12I protein exhibits significant amino acid sequence similarity to the E5 oncoprotein of bovine papillomavirus type 1 (BPV-1). Both proteins are very hydrophobic, contain a glutamine residue in the middle of a potential transmembrane region(s), and are localized in similar cellular compartments. Because of these observations, we investigated whether the p12I resemblance to E5 correlated with a similarity in their biological behavior. We expressed the p12I protein to evaluate its ability to functionally cooperate with the BPV-1 E5 oncoprotein and to bind to a cellular target of the E5 protein, the 16K component of the vacuolar H+ ATPase. Cotransfection of the mouse C127 cell line with the p12I and E5 cDNAs showed that although p12I alone could not induce focus formation, it strongly potentiated the transforming activity of E5. In addition, the p12I protein bound to the 16K protein as efficiently as the E5 protein. These findings might provide new insight for potential mechanisms of HTLV-I transformation and suggest that p12I and E5 represent an example of convergent evolution between RNA and DNA viruses.
Franchini
G
G
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
Mulloy
J C
JC
Koralnik
I J
IJ
Lo Monico
A
A
Sparkowski
J J
JJ
Andresson
T
T
Goldstein
D J
DJ
Schlegel
R
R
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D052688:Bovine papillomavirus 1 / Q000235:genetics; D002460:Cell Line; D002472:Cell Transformation, Viral; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014617:Vacuoles / Q000201:enzymology; D054334:Viral Regulatory and Accessory Proteins
D009856:Oncogene Proteins, Viral; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C054304:oncogene protein E5, Bovine papillomavirus type 1; C084305:p12I protein, Human T-lymphotropic virus 1; D006180:Proton-Translocating ATPases