According to previous models, the tumor suppressor protein Merlin, encoded by the neurofibromatosis type 2 (NF2) gene, inhibits mitotic signaling at or near the cell membrane. However, in the cover story of the February 19, 2010 issue of Cell, researchers present evidence supporting the proposal that Merlin actually suppresses tumorigenesis by translocating to the nucleus where it binds to the E3 ubiquitin ligase CRL4DCAF1 and inhibits its ability to ubiquitylate target proteins. The researchers stated that multiple converging lines of evidence now indicate that Merlin's inhibition of CRL4DCAF1 activity is required to induce growth arrest and suppress tumorigenesis. Notably, the scientists showed that the tumor-derived mutations in NF2 that they examined invariably disrupted Merlin’s ability to interact with or inhibit CRL4DCAF1. This represents a new mechanism for the production of certain tumors in the brain. These tumors occur in a range of cell types, including Schwann cells. Schwann cells produce the sheaths that surround and insulate neurons. The tumors most often occur spontaneously, but can also occur in significant numbers as part of the inherited disease NF2. In NF2, the sheer number of tumors can overwhelm a patient, often leading to severe disability and eventually death. Patients can suffer from 20 to 30 tumors at any one time, and the condition typically affects older children and young adults. No therapy, other than invasive (radio) surgery which is aimed at a single tumor and which may not eradicate the full extent of the tumors, exists. NF2 is estimated to affect one in every 2,500 people worldwide. It can affect any family, regardless of past history, through gene mutation, and currently there is no cure. Dr.
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