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. Despite significant obstacles imposed by the Covid 19 pandemic, we made substantial progress addressing Aim 1d. We identified a cohort of proteins that are co-proximal to both Merlin and ASPP2 and require Merlin to associate with ASPP2, in both growing and contact inhibited cells. In doing so we validated a more sensitive and powerful proximity biotinlyation technique and generated data that will inform the work moving forward.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2021
- Accession Number
- AD1147435
Entities
People
- Robert F. Henningan
Organizations
- Cincinnati Children's Hospital Medical Center