Lymphotoxin-beta receptor mediates NEMO-independent NF-kappaB activation.
Lymphotoxin-beta receptor (LTbetaR) is a member of the tumor necrosis factor receptor (TNFR) superfamily that activates nuclear factor-kappaB (NF-kappaB) through the IkappaB kinase (IKK) complex, the core of which is comprised of IKK1, IKK2 and NF-kappaB essential modulator (NEMO). We demonstrate here that the LTbetaR signaling to NF-kappaB activation does not necessarily require NEMO, which is essential for TNFR signaling. In the absence of NEMO, the p50 and RelB, but not RelA subunits of NF-kappaB are found in the nuclear DNA binding complexes induced by the LTbetaR signaling. Our results thus disclose NEMO-independent NF-kappaB activation by LTbetaR.
Saitoh
Tatsuya
T
Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Nakano
Hiroyasu
H
Yamamoto
Naoki
N
Yamaoka
Shoji
S
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D051550:I-kappa B Kinase; D053259:Lymphotoxin beta Receptor; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2; D048015:TNF Receptor-Associated Factor 5; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018124:Receptors, Tumor Necrosis Factor; C497594:Relb protein, mouse; D047992:TNF Receptor-Associated Factor 2; D048015:TNF Receptor-Associated Factor 5; D051996:Transcription Factor RelA; D014157:Transcription Factors; D051841:Transcription Factor RelB; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse