Constitutive CD40 signaling phenocopies the transforming function of the Epstein-Barr virus oncoprotein LMP1 in vitro.
The oncoprotein LMP1 mimics an activated CD40 receptor, yet it is not known whether constitutive CD40 signaling, like LMP1, is sufficient to transform cells. Here we demonstrate that constitutive activation of the CD40 pathway by a chimeric LMP1CD40 molecule resembles the transforming function of LMP1 in inducing loss of contact inhibition and anchorage independent growth of Rat1 fibroblasts. Rat1 transformation correlates with the expression level of LMP1CD40 and depends on its ability to oligomerize. Our data provide direct evidence for the oncogenic potential of the CD40 signaling pathway, which is also established as a model-mechanism for LMP1-induced transformation.
Hatzivassiliou
Eudoxia G
EG
Institute of Immunology, Biomedical Sciences Research Center Al. Fleming, 34 Al. Fleming Str., Vari 16672, Greece.
Kieff
Elliott
E
Mosialos
George
G
D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism*; D002460:Cell Line; D002472:Cell Transformation, Viral / Q000235:genetics; D003260:Contact Inhibition / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
D019013:CD40 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins