IRF-2 regulates NF-kappaB activity by modulating the subcellular localization of NF-kappaB.
Nuclear Factor-kappa B (NF-kappaB) is a transcription factor essential to the control of cell proliferation, survival, differentiation, immune response, and inflammation. Constitutive NF-kappaB activation has been observed in a broad variety of solid tumors and hematological malignancies, which suggests that NF-kappaB signaling may perform a critical role in the development of human cancers. Interferon regulatory factor-2 (IRF-2), an antagonistic transcriptional repressor of IRF-1, evidences oncogenic potential, but little is currently known regarding the mechanism underlying the oncogenic activities of IRF-2. In this study, we report that IRF-2 recruits RelA/p65 transcription factors into the nucleus via physical interaction. While the nuclear recruitment of RelA by IRF-2 augments TNFalpha-induced NF-kappaB dependent transcription, the N-terminal truncated mutant form of IRF-2 inhibits the nuclear localization of RelA, and thus interferes with NF-kappaB activation. Furthermore, the knockdown of IRF-2 by IRF-2 siRNA attenuates TNFalpha-induced NF-kappaB dependent transcription by inhibiting the nuclear localization of RelA. Thus, these results show that IRF-2 regulates NF-kappaB activity via the modulation of NF-kappaB subcellular localization.
Chae
Myounghee
M
Korea Basic Science Institute, Gwangju Center, 300, Yongbong-Dong, Book-Ku, Gwangju 500-757, Republic of Korea.
Kim
Kwangsoo
K
Park
Sun-Mi
SM
Jang
Ik-Soon
IS
Seo
Taegun
T
Kim
Dong-Min
DM
Kim
Il-Chul
IC
Lee
Je-Ho
JH
Park
Junsoo
J
D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D050836:Interferon Regulatory Factor-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017384:Sequence Deletion; D051996:Transcription Factor RelA / Q000032:analysis / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D050836:Interferon Regulatory Factor-2; C498143:RELA protein, human; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha