Molecules and Cells · 2002 · 34 citations · 32 references
Life SciencesCell BiologyOncologyCell ProliferationCell SignalingSignal TransductionCancer Cell SignalingCell Proliferation ControlOncogenic Signaling PathwaysRas Family OncogenesSignal Transduction In CancerTumor Suppressor GenesActivator Protein 1 ActivationAp-1 Transcriptional ControlCell Growth RegulationE2f Transcription ControlE2f Transcription Factor ActivationE2f Transcription Factor RegulationE2f Transcription FactorsRas Signaling
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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