Inhibition of NF-kappaB activation by merlin.
The neurofibromatosis type 2 (NF2) gene encodes an ezrin-radixin-moesin (ERM) related protein, referred to as either merlin or schwannomin, that is known to be a tumor suppressor. NF-kappaB signaling is known to be important for controlling cellular proliferation and protecting against apoptosis. In this report, merlin was demonstrated to be effective in suppressing the NF-kappaB signaling pathway in NIH3T3 and C6 cells. In addition, merlin blocked the tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB-DNA binding mediated via the inhibition of degradation of IkappaBalpha and blocked the activation of NF-kappaB-dependent transcription. A reporter gene assay using deletion mutants of NF2 showed that the N-terminus (amino acids 1-130) of merlin may be important for its inhibition of NF-kappaB activation. These results show that merlin acts as a negative regulator of the NF-kappaB signaling pathway.
Kim
Jae Young
JY
Department of Pharmacology, The Catholic University of Korea, 505 Banpo-dong, Socho-ku, 137-701, Seoul, Republic of Korea.
Kim
Hongtae
H
Jeun
Sin-Soo
SS
Rha
Suk Joo
SJ
Kim
Young Hoon
YH
Ko
Young Jin
YJ
Won
Jonghwa
J
Lee
Kweon-Haeng
KH
Rha
Hyoung Kyun
HK
Wang
Young-Pil
YP
D016475:3T3 Cells; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D025581:Neurofibromin 2 / Q000737:chemistry / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D017434:Protein Structure, Tertiary; D051381:Rats; D015398:Signal Transduction; D051996:Transcription Factor RelA; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000097782:NF-kappaB-Inducing Kinase
D004268:DNA-Binding Proteins; D051550:I-kappa B Kinase; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D025581:Neurofibromin 2; D017346:Protein Serine-Threonine Kinases; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000097782:NF-kappaB-Inducing Kinase; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; C496564:Chuk protein, mouse; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse