Inhibition of ras-mediated activator protein 1 activity and cell growth by merlin

Hongtae Kim, Jung Yeon Lim, Young Hoon Kim, Hyun Kim, Sun-Hwa Park, Kweon-Haeng Lee, Hoon Han, Sin-Soo Jeun, Joung H Lee, Hyoung Kyun Rha
Molecules and Cells 2002 August 31, 14 (1): 108-14
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.

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