Inhibition of ras-mediated activator protein 1 activity and cell growth by merlin.
The neurofibromatosis type2 (NF2) gene encodes an intracellular-associated protein that is referred to as either merlin or schwannomin. Merlin/Schwannomin is a tumor suppressor protein that has been reported to block the Ras-mediated cell proliferation and -anchorage-independent cell growth. However, its inhibitory mechanism is uncertain. In this report, merlin was demonstrated to be effective in suppressing Ras-induced foci-formation and its associated AP-1 activity in NIH3T3cells. In addition, merlin blocked Ras-induced Rb phosphorylation, and inhibited the increase of cyclin D1 levels. It also blocked E2F-1-dependent transcription. These results suggest that merlin inhibits abnormal cell proliferation which is activated via Ras by repressing Rb phosphorylation, blocking the increase of the cyclin D1 protein level, and inhibiting the activation of AP-1- and E2F-1-dependent transcription in NIH3T3 cells.
Kim
Hongtae
H
Neuroscience Genome Research Center, The Catholic University of Korea, Seoul.
Lim
Jung Yeon
JY
Kim
Young Hoon
YH
Kim
Hyun
H
Park
Sun-Hwa
SH
Lee
Kweon-Haeng
KH
Han
Hoon
H
Jeun
Sin-Soo
SS
Lee
Joung H
JH
Rha
Hyoung Kyun
HK
D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D019938:Cyclin D1 / Q000378:metabolism; D051379:Mice; D025581:Neurofibromin 2 / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D025581:Neurofibromin 2; D016160:Retinoblastoma Protein; D018808:Transcription Factor AP-1; D019938:Cyclin D1; D018631:ras Proteins