TNIP1 affects proliferation, apoptosis and migration of Human Embryonic Kidney 293 cells

Abstract

TNIP1 is a protein associated with autophagy and inflammation, which is ubiquitously expressed in the brain. It mediates extracellular signals such as growth factor signaling, influences nuclear expression patterns driven by NF-kappaB transcriptional regulation and exhibits both pro- and anti-apoptotic properties. The involvement in these cellular pathways deems it an attractive candidate gene for neurodegenerative disease pathogenesis. In fact, gene variations of TNIP1 have recently been linked to both amyotrophic lateral sclerosis and Alzheimer’s disease. Moreover, TNIP1 has been shown to interact with Engrailed-2, a transcription factor associated with autism spectrum disorder (ASD). While the linkage between ASD and TNIP1 is currently low, the fact that TNIP1 has long been considered a pleiotropic risk locus for autoimmune and chronic inflammatory disorders, is intriguing, considering these are common comorbidities of ASD. Despite the plethora of links to cell death and inflammatory processes in the body, exact cellular and molecular pathways are not yet elucidated. In addition, proper animal models are not available thus far. Therefore, it was the aim of this thesis, to establish genetic tools to overexpress and repress TNIP1. Using these genetic tools, I was able to demonstrate that TNIP1 expression can be altered in the mammalian cell line HEK 293. I was able to identify an antibody suitable to track changes in TNIP1 expression and I demonstrated that the alteration of TNIP1 expression in HEK 293 cells enhanced apoptosis and diminished both proliferation and cellular migration. Having these tools at hand now paves the way not only for the manipulation of neuronal cell cultures, but also for the investigation of TNIP1 expression patterns in brain tissue. It will also allow for the characterization of animal models, to hopefully provide further insights into TNIP1 mediated neurodegenerative processes.