RelA suppresses the Wnt/beta-catenin pathway without exerting trans-acting transcriptional ability.
Several cellular signaling systems exhibit cross talk. Cross talk seems to play an important role in modifying signal effects. In vertebrates, the nuclear factor kappa B (NF-kappaB) signaling pathway plays important roles in immune response, inflammation and apoptosis. Meanwhile, the Wnt/beta-catenin signaling pathway is involved in oncogenesis and development. We show here that RelA, a component of NF-kappaB, specifically suppressed beta-catenin/Tcf-dependent transcription. This suppression did not depend on the trans-acting transcriptional ability of RelA. Furthermore, RelA neither affected the nuclear import of beta-catenin nor the DNA binding ability of the beta-catenin/Tcf complex, suggesting that NF-kappaB modifies this signaling pathway after the binding of the beta-catenin/Tcf complex with target DNA.
Masui
Osamu
O
Department of Viral Oncology, Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Ueda
Yoshihide
Y
Tsumura
Akiko
A
Koyanagi
Michiyo
M
Hijikata
Makoto
M
Shimotohno
Kunitada
K
D000818:Animals; D019556:COS Cells; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin