Molecular Function of Midnolin and Its Relevance to Parkinson's Disease.

Abstract

Midnolin (Midn) was originally discovered as a gene expressed specifically in the mouse midbrain at the embryonic developmental stage; MIDN was localized in the nucleus/nucleolus. Although the pathophysiological roles of MIDN remained largely unknown for many years after its discovery, its molecular functions and relevance to diseases have gradually become clearer. In PC12 cells, a rat neuronal model cell line, liquidity factors that are necessary for neurite outgrowth are reported to induce Midn gene expression. In addition, MIDN is required for E3 ubiquitin-protein ligase parkin expression, suggesting that MIDN is important for the development and maintenance of neuronal functions. Notably, it was recently reported that MIDN plays fundamental roles in the ubiquitin-independent proteasomal degradation of various nuclear proteins and transcription factors. Regarding the relationship between MIDN and diseases, copy number loss of MIDN is associated with Parkinson's disease, suggesting that MIDN is a genetic risk factor for this disease. In addition, MIDN is relevant to many types of malignant cancer, including B-cell lymphoma and liver cancer. Thus, MIDN is an essential molecule for the maintenance of homeostasis, and its functional disorder triggers multiple diseases depending on the affected tissues/organs. MIDN therefore shows promise as a potential therapeutic target and prognostic biomarker.