Regulation of Translation by NF1
Abstract
Neurofibromatosis Type I is cancer predisposition syndrome characterized by neurofibromas, benign tumors derived from peripheral nerve Schwann cells. The gene that is mutated to cause Neurofibromatosis Type I, NF1, encodes a 319 kDa protein called neurofibromin (NF1). NF1 negatively regulates members of Ras superfamily, oncogenes that are critical to the development of cancer. To gain insight into new NF1 functions, we performed experiments to identify the proteins with which it interacts. We found that NF1 associates with ribosomes suggesting the hypothesis that NF1 may regulate gene expression at the level of translation. We proposed to measure the levels of both mRNA and proteins for all genes in presence and absence of NF1 using the powerful and sensitive methods RNAseq, TRAPseq and SILAC mass spec analysis. These experiments are ongoing. We have completed the RNAseq of NF1 null iHSC-1 lambda delta NF1#1 and scrambled control iHSC-1 lambda ScrP cells. This part of the project identified a substantial number of differentially expressed genes, suggesting that loss of NF1 is necessary and sufficient to suppress these genes at the level of transcription. Work of the total proteome and the TAPseq experiments are proceeding after preliminary experiments demonstrated the necessity that we switch to a DOX inducible NF1 expression system. This delay should not prevent us from testing the hypothesis that NF1 regulates expression at the level of translation. The results from these experiments will be a critical tool in understanding the function of NF1 and the consequences of NF1mutation in the development of Neurofibromatosis Type I.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1202727
Entities
People
- Robert F Hennigan