Integrated Proteomics Identified Novel Activation of Dynein IC2-GR-COX-1 Signaling in Neurofibromatosis Type I (NF1) Disease

Neurofibromatosis type 1 (NF1) tumor suppressor gene product, neurofibromin, functions in part as a Ras-GAP, and though its loss is implicated in the neuronal abnor-mality of NF1 patients, its precise cellular function re-mains unclear. To study the molecular mechanism of NF1 pathogenesis, we prepared NF1 gene knockdown (KD) PC12 cells, as a NF1 disease model, and analyzed their molecular (gene and protein) expression profiles with a unique integrated proteomics approach, comprising iTRAQ, 2D-DIGE, and DNA microarrays, using an inte-grated protein and gene expression analysis chart (iPEACH). In NF1-KD PC12 cells showing abnormal neu-ronal differentiation after NGF treatment, of 3198 mole-cules quantitatively identified and listed in iPEACH, 97 molecules continuously up- or down-regulated over tim