Merlin-ASPP2 Tumor Suppressor Interactions in Mechanosensory Signal Transduction from Schwann Cell Junctions in Neurofibromatosis Type 2
Abstract
Neurofibromatosis Type 2 is an inherited disease characterized by bilateral schwannomas that are caused by inactivation of the product of the NF2 tumor suppressor gene, Merlin. We used a powerful new technique, proximity biotinylation, to identify a new merlin binding protein, ASPP2, a tumor suppressor that interacts with a range of oncogenic signal transduction molecules. We hypothesized that merlin-ASPP2 interactions are required to regulate mechano-sensory signal transduction. To test this, we will determine if merlin-ASPP2 interaction is required from merlin function and identify the merlin and ASPP2 binding proteins that connect them with upstream cell junction complexes. We have identified Merlin as necessary for ASPP2 localization thus identifying it as a critical binding partner for ASPP2 function. Furthermore, we identified a basic biochemical mechanism by which Merlin is activated in response to PIP2. We have also greatly expanded our understanding of the Merlin interactome and identified novel binding partners that may represent a novel mechanism of action.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2023
- Accession Number
- AD1213436
Entities
People
- Robert F Hennigan