Epstein-Barr virus LMP2A bypasses p53 inactivation in a MYC model of lymphomagenesis.
Although Epstein-Barr virus (EBV) is linked to Burkitt's lymphoma (BL), the role of the virus in lymphomagenesis is unclear. LMP2A, encoded by EBV, can be detected in BL biopsies and has prosurvival functions. We generated mice expressing MYC and LMP2A in B cells. LMP2A/lambda-MYC mice show greatly accelerated tumor onset. Similar to previous work, we found p53 mutations in lambda-MYC tumors; however, we detected no mutations in the rapidly arising LMP2A/lambda-MYC tumors. We further demonstrate that the p53 pathway is functionally intact in LMP2A/lambda-MYC tumors, which have increased levels of PUMA and sensitivity to p53 activation by Nutlin. This work shows that LMP2A can permit tumorigenesis in the presence of an intact p53 pathway, identifying an important contribution of EBV to BL.
Bieging
Kathryn T
KT
Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Amick
Alexandra C
AC
Longnecker
Richard
R
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002051:Burkitt Lymphoma / Q000209:etiology* / Q000235:genetics / Q000821:virology; D004195:Disease Models, Animal; D005814:Genes, Viral; D016259:Genes, myc; D016158:Genes, p53; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D014763:Viral Matrix Proteins / Q000235:genetics* / Q000502:physiology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins