Characterization of an E3 Ubiquitin Ligase that Degrades Neurofibromin in Vitro and Vivo
Abstract
Neurofibromatosis type 1 (NF1) patients are predisposed to various clinical complications, including benign and malignant tumors in both the peripheral nervous system and central nervous system. Furthermore, Nf1 patients are at high risks for non- tumor related symptoms such as neurocognitive and motor deficits, structural brain defects and bone abnormalities. The proposed studies attempt to provide important insights into one of the critical questions in the field of NF1 molecular mechanisms regulating neurofibromin degradation. The objectives of this proposal are to utilize a newly established mouse model to (1) elucidate a positive feedback loop in the FBXW7/NF1/ERK axis in vivo and to (2) seek novel therapeutic strategies for NF1 haploinsufficient lesions various clinical manifestations. To test this model, we propose two hypotheses: (1) Neurofibromin is an SCFFbxw7 substrate in vivo and (2) a high level of Erk activation is a specific context contributing to Nf1 haploinsufficient diseases. We propose the following two specific aims to test these hypotheses.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2012
- Accession Number
- ADA583362
Entities
People
- Yuan Zhu
Organizations
- University of Michigan