A tumor-suppressor function for NFATc3 in T-cell lymphomagenesis by murine leukemia virus.
Nuclear factor of activated T cell (NFAT) transcription factors play a central role in differentiation, activation, and elimination of lymphocytes. We here report on the finding of provirus integration into the Nfatc3 locus in T-cell lymphomas induced by the murine lymphomagenic retrovirus SL3-3 and show that NFATc3 expression is repressed in these lymphomas. The provirus insertions are positioned close to the Nfatc3 promoter or a putative polyadenylated RNA (polyA) region. Furthermore, we demonstrate that NFATc3-deficient mice infected with SL3-3 develop T-cell lymphomas faster and with higher frequencies than wild-type mice or NFATc2-deficient mice. These results identify NFATc3 as a tumor suppressor for the development of murine T-cell lymphomas induced by the retrovirus SL3-3.
Glud
Sys Zoffmann
SZ
Department of Molecular Biology, University of Aarhus, Denmark.
Sørensen
Annette Balle
AB
Andrulis
Mindaugas
M
Wang
Bruce
B
Kondo
Eisaku
E
Jessen
Randi
R
Krenacs
Laszlo
L
Stelkovics
Eva
E
Wabl
Matthias
M
Serfling
Edgar
E
Palmetshofer
Alois
A
Pedersen
Finn Skou
FS
D000818:Animals; D009052:Leukemia Virus, Murine / Q000235:genetics / Q000276:immunology*; D007942:Leukemia, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D050778:NFATC Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000276:immunology*; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016662:Virus Integration / Q000276:immunology
D050778:NFATC Transcription Factors; C494009:Nfatc3 protein, mouse; D025521:Tumor Suppressor Proteins