Interaction between Hippo Pathway Elements and the E3‐ligase CHIP regulate a potential marker of Alzheimer`s disease

Abstract Background The transcriptional coactivator YAP‐1, a known CHIP substrate that has a role in the regulation of adaptation to cellular stress, cell size and metabolism, was investigated as a potential link between CHIP and VGF. Method Previously, CRISPR‐Cas9 method was used to create CHIP KO neuroblastoma cell line. Then, SWATH‐MS experiment was applied to get proteomic data of CHIP KO and WT neuroblastoma cells. Validation of data analysis done by immunoblot and IF. Following gene manipulations were applied by transfection of RNAi and following assessments done by immunoblot and IF. Result According to our proteomic analysis, CHIP KO neuroblastoma cells have 10X more VGF protein than isogenic WT cells. YAP1 was expressed at high levels in the nucleus of CHIP KO neuroblastoma cells and manipulation of YAP1 impacted on the expression of VGF. Conclusion As VGF is an Alzheimer’s disease biomarker, discovering mechanisms of VGF regulation could support efforts to find new targets for the development of disease modifying drugs.