Truncated form of the Epstein-Barr virus protein EBNA-LP protects against caspase-dependent apoptosis by inhibiting protein phosphatase 2A.
The Epstein-Barr virus (EBV)-encoded leader protein, EBNA-LP, strongly activates the EBNA2-mediated transcriptional activation of cellular and viral genes and is therefore important for EBV-induced B-cell transformation. However, a truncated form of EBNA-LP is produced in cells infected with variant EBV strains lacking EBNA2 due to a genetic deletion. The function of this truncated form is unknown. We show here that some Burkitt's lymphoma cells harboring defective EBV strains are specifically resistant to the caspase-dependent apoptosis induced by verotoxin 1 (VT-1) or staurosporine. These cells produced low-molecular-weight Y1Y2-truncated isoforms of EBNA-LP, which were partly localized in the cytoplasm. The transfection of sensitive cells with constructs encoding truncated EBNA-LP isoforms, but not full-length EBNA-LP, induced resistance to caspase-mediated apoptosis. Furthermore, VT-1 induced protein phosphatase 2A (PP2A) activation in sensitive cells but not in resistant cells, in which the truncated EBNA-LP interacted with this protein. Thus, the resistance to apoptosis observed in cells harboring defective EBV strains most probably results from the inactivation of PP2A via interactions with low-molecular-weight Y1Y2-truncated EBNA-LP isoforms.
Garibal
Julie
J
UMR 8126 CNRS, University Paris-Sud, Institut Gustave Roussy, Rue Camille Desmoulins, 94805 Villejuif cedex, France.
Hollville
Emilie
E
Bell
Andrew I
AI
Kelly
Gemma L
GL
Renouf
Benjamin
B
Kawaguchi
Yasushi
Y
Rickinson
Alan B
AB
Wiels
Joëlle
J
D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D054648:Protein Phosphatase 2; D014162:Transfection; D014764:Viral Proteins / Q000737:chemistry / Q000502:physiology*
C402640:EBNA-LP protein, Human herpesvirus 4; D014764:Viral Proteins; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D020169:Caspases