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Authors & Affiliations
Stephan Schieren, Joachim Fandrey, Tristan Leu
Abstract
Primary cilia are non-motile, antenna-like organelles present on the surface of most human cell types. They play an essential role in processes such as proliferation, apoptosis, migration, and differentiation. Primary cilia are involved in many signalling pathways, including Hedgehog, WNT, and TGF-β. Consequently, ciliary dysfunctions lead to severe diseases known as ciliopathies.The formation and function of primary cilia are closely associated with the cell's oxygen supply. Proper cell function requires adequate oxygen levels, so cells must respond quickly to any deviation from the norm. The hypoxic response is influenced by hypoxia-inducible factors (HIFs).HIF accumulates at/in primary cilia under hypoxia and affect different target genes. Recent studies have shown that HIF-2α affects the MEK/ERK signalling pathway via the primary cilia. Under hypoxic conditions, primary cilia elongate and HIF-2α translocates into the cilia through the ciliary gate.Our study focuses on the effect of hypoxia on the activity of the ciliary proteasome by analyzing the localization and intensity of β-catenin and ubiquitin in primary cilia using immunofluorescence microscopy. The ciliary proteasome is a specialized proteasome that is exclusively regulated by ciliary proteins. Previous studies have shown that Gli3, a protein in the Hedgehog signalling pathway, is proteasomally cleaved in primary cilia. The functions of this proteasome in relation to HIF and hypoxia are not known and part of this study. Additionally, we are examining different HIF target genes to determine if there are varying levels of gene expression under hypoxia influenced by the ciliary proteasome.