TNIP1 As A Potential Factor In Neuronal Survival, Growth and Differentiation in the Cerebellar Cortex

Abstract Tumor Necrosis Factor-Induced Protein 1 (TNIP1) is a well-known ubiquitin-binding signaling molecule involved in innate and adaptive inflammatory processes. It has been implicated in diverse immunological diseases, but also associated with various neuro-psychiatric conditions, including Alzheimer’s disease, glioma formation, and demyelination. However, a systematic analysis of TNIP1 expression and function in the central nervous system is missing. Here, we combine immunohistochemical staining, Western blotting, quantitative PCR and the re-analysis of publicly available single cell- and in situ hybridization-mRNA datasets to document the expression of TNIP1 in the developing and adult murine cerebellum. We document that TNIP1 is broadly expressed in cerebellar neurons and macroglial cells, where it is localized to discrete puncta within cell nuclei and somata, including Purkinje cell dendrites. Both TNIP1 and its mRNA are developmentally regulated in the early postnatal cerebellum, and levels of the latter vary systematically across the cell cycle. Consistently, overexpression of TNIP1 in human embryonic kidney cells inhibits proliferation and activates cleaved caspase-3 expression. These observations support a role for TNIP1 in neur(on)al development and function and establish a paradigm to study the mechanistic basis of its function in the normal and diseased nervous system.