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Foundation Funded Breakthrough NF2 Research Published in Top Journal ‘Cell’

By February 18, 2010December 18th, 2023Awareness, NF2-SWN, Science & Research

As we have reported, some major advances have been made recently to unravel the functioning of merlin, the protein made by the NF2 gene.  Merlin is a tumor suppressor protein and it does not operate properly in patients with NF2, which leads to the formation of schwannomas and meningioma tumors.  However its not obvious how merlin actually ‘moves around’ and operates inside the cell; the traditional view has held that merlin protein acts at the cell membrane. Why is this important? Because we need to understand merlin function so that we can appropriately target drugs to restore and ‘normalize’ its activity in NF2 tumors as a drug treatment approach.

Today, a paper in the top-notch journal ‘Cell’ (link to summary) authored by Children’s Tumor Foundation funded Young Investigator Awardee Wei Li (Memorial Sloan Kettering Cancer Center) reports that merlin in fact accumulates in the cell nucleus, and stops cells from dividing by binding to a called E3 ubiquitin ligase CRL4-DCAF1 (‘DCAF1’).  The group showed that in cells lacking functional merlin (i.e. a model of NF2),  knocking down the ligase suppresses the high level of cell growth that leads to tumor formation. Most significantly when the group used a drug to block DCAF1 activity in human NF2 schwannoma tumor cells the cells returned to more normalized, non-tumor like levels of growth. This breakthrough finding opens up a new candidate drug target for the treatment of NF2 tumors – especially becausemany patients have gene mutations that affect this cell signaling pathway at various levels.

The publication of this work in ‘Cell’ is recognition of its landmark status. The publishing research team included many of our colleagues: the team was headed by Dr. Filippo Giancotti (a member of the NF Preclinical Consortium Oversight Committee), and included past DDI Award recipient Dr. Oliver Hanemann (Peninsula Medical School) and current DDI Awardee and NF Preclinical Consortium site director Dr. Marco Giovannini (House Ear Institute).