Structural Basis of Merlin Tumor Suppressor Functions in Neurofibromatosis-2
Abstract
The development of effective and safe therapeutics that can be used to combat the debilitating and incurable malignancies that are associated with neurofibromatosis type II (NF2) clearly requires a detailed understanding of the underlying molecular basis of this disease. NF2 is the gene that encodes the cytoskeletal tumor suppressor protein merlin, which is required for the development and stabilization of cell-cell contacts that are mediated by specialized cell surface structures called adherens junctions. Lossof- function mutations of merlin are the hallmark of NF2, and these mutations disable its functions in controlling adherens junctions, provoking uncontrolled cell growth and leading to the development of ultimately lethal tumors, including schwannoma, meningioma, and mesothelioma. This award allowed us to perform a series of structural and biochemical studies that provide the foundation for developing small molecule therapeutic agents that bind and reactivate the tumor suppressor activity of mutated merlin.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2014
- Accession Number
- ADA613321
Entities
People
- Tina Izard
Organizations
- Scripps Research