SUMOylated IRF-1 shows oncogenic potential by mimicking IRF-2.
Interferon regulatory factor-1 (IRF-1) is an interferon-induced transcriptional activator that suppresses tumors by impeding cell proliferation. Recently, we demonstrated that the level of SUMOylated IRF-1 is elevated in tumor cells, and that SUMOylation of IRF-1 attenuates its tumor-suppressive function. Here we report that SUMOylated IRF-1 mimics IRF-2, an antagonistic repressor, and shows oncogenic potential. To demonstrate the role of SUMOylated IRF-1 in tumorigenesis, we used SUMO-IRF-1 recombinant protein. Stable expression of SUMO-IRF-1 in NIH3T3 cells resulted in focus formation and anchorage-independent growth in soft agar. Inoculation of SUMO-IRF-1-transfected cells into athymic nude mice resulted in tumor formation and infiltration of adipose tissues. Finally, we demonstrated that SUMO-IRF-1 transforms NIH3T3 cells in a dose-dependent manner suggesting that SUMOylated IRF-1 may act as an oncogenic protein in tumor cells.
Park
Sun-Mi
SM
Yonsei University, Division of Biological Science and Technology, Wonju 220-100, Republic of Korea.
Chae
Myounghee
M
Kim
Bo-Kyoung
BK
Seo
Taegun
T
Jang
Ik-Soon
IS
Choi
Jong-Soon
JS
Kim
Il-Chul
IC
Lee
Je-Ho
JH
Park
Junsoo
J
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism*; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D041681:NIH 3T3 Cells; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D014162:Transfection
D050856:Interferon Regulatory Factor-1; D050836:Interferon Regulatory Factor-2; D011994:Recombinant Proteins; D025841:Small Ubiquitin-Related Modifier Proteins