Identification of Novel Signaling Pathways in NF2
Abstract
Schwannomas are benign peripheral nerve tumors that are initiated by biallelic mutation of the NF2 tumor suppressor gene,resulting in loss of function of the NF2 gene product, merlin. Loss of merlin drives tumor formation but there is no consensus on the mechanism of merlins tumor suppressor function. Merlin has no intrinsic catalytic activity, its function regulated by the proteins with which it interacts. We used proximity biotinylation and direct binding assays to perform a global proteomic analysis that identified 52 merlin-associated proteins. The majority of merlin proximal proteins are components of cell junctional signaling complexes including actin binding proteins and members of the Hippo pathway. This pattern of protein interactions suggests that merlin functions as part of a mechano-sensory signal transduction network. We hypothesize that the loss of merlin destabilizes or impairs assembly of these structures, causing abnormal, cancer causing signals. To test this hypothesis, we will again use proximity biotinylation to look for changes in key cell junction components in the presence or absence of merlin. We expect that the experiments described in this proposal will yield greater insight into consequences of the loss of merlin that may be used to devise therapies to treat this disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2019
- Accession Number
- AD1097585
Entities
People
- Robert F Hennigan