Neurofibromatosis type 2 protein, NF2: an uncoventional cell cycle regulator

Neurofibromatosis type 2 protein (NF2) is an underappreciated tumor suppressor involved in a broad range of nervous system tumors. Inactivation of the NF2 gene leads to neurofibromatosis type-2, which is characterized by multiple benign nervous system tumors and mutations in the gene have been demonstrated in many other tumor types as well. All tumors, regardless of location or grade, lack a fundamental control over cell cycle progression. Historically, NF2 is an unconventional tumor suppressor protein in that it does not directly influence the cell cycle. NF2 links receptors at the plasma membrane to their cytoplasmic kinases to facilitate contact inhibition. However, NF2 can also interact with an array of cytoplasmic and nuclear proteins that affect cell cycle progression. Furthermore, through some of these pathways, NF2 may reverse the functional inhibition of conventional tumor suppressor pathways. Here we review mechanisms utilized by NF2 to regain control of the cell cycle.