Neurofibromatosis type 1 (NF1) is the most common genetic disease in humans with a predisposition to cancer. NF1 is caused by mutations of NF1 tumor suppressor gene that functions as GAP for Ras. The molecular mechanism of NF1 haploinsufficiency has unknown. Yet, the primary mechanism of haploinsufficiency is due to insufficient protein level.
Neurofibromin expression is not only diminished by genetic loss and epigenetic lesion but also the protein itself is a target for accelerated degradation. In light of the NF1 haploinsufficient degradation by Ubiquitin-Proteasome Pathway (UPP) is clinically importance. However, little is known about the molecular mechanism for degradation of neurofibromin by Ubiquitin-Proteasome Pathway.
The goal of study is to contribute to the development of new therapeutic approaches to treat NF1 syndrome where neurofibromin is chronically destabilized.
