Biology subjects

Elbaek, C. R.

Publications and source records attributed to Elbaek, C. R..

2 recordsLinked to original sources

bioRxiv2025

Multi-omics analysis of keratinocytes reveals dermokine-dependent regulation of cell-cell adhesion via p120

Loss of keratinocyte differentiation is a leading cause in several skin diseases and needs to be controlled in adult homeostasis by for instance growth factors and proteases. Among them, we studied the role of isoform-rich dermokine - a wound- and tumour-related matrix metalloproteinase 10 substrate - via functional multi-omics. We generated dermokine isoform-dependent keratinocyte knockouts and three dimensional (3D) organotypic skin cultures and analyzed changes in their proteome and phosphoproteome by quantitative mass spectrometry. Through functional in vitro assays, we demonstrate that in the absence of dermokine-isoforms, p120 phosphorylation increases while cell-cell adhesion decreases in keratinocytes. Furthermore, we validate the link between decreased dermokine expression and phosphorylated p120-mediated adhesion in non-healing wounds samples derived from patients. Our data reveal a novel dermokine-p120-dependent cell-cell adhesion phenotype in keratinocytes and improve our understanding of wound-edge keratinocytes, expanding the hypothesis that dysregulated wounds resemble cancer.

cell biology↗

bioRxiv2024

M1-linked Ubiquitination by LUBAC Regulates AMPK Activity and the Response to Energetic Stress

Methionine-1 (M1)-linked ubiquitin chains, assembled by the ubiquitin ligase LUBAC and cleaved by the deubiquitinase OTULIN, are critical regulators of inflammation and immune homeostasis. Genetic loss of either LUBAC or OTULIN causes autoinflammatory syndromes, which are associated with defects in glycogen and lipid metabolism. However, how LUBAC and OTULIN regulate metabolic signalling remains unknown. Here, we demonstrate that LUBAC promotes, while OTULIN restricts, activation of the key metabolic regulator AMP-activated protein kinase (AMPK) in cells, mice, and human samples. LUBAC and OTULIN interact with AMPK, control its M1-ubiquitination, and regulate its activation in response to glucose starvation and allosteric activation. During starvation, LUBAC deficiency impairs autophagy induction and hinders the shift from oxidative phosphorylation to glycolysis. Strikingly, LUBAC-deficient Drosophila have a strongly reduced survival rate after starvation. Our work identifies LUBAC and OTULIN as physiological regulators of AMPK, providing the first mechanism by which M1-linked ubiquitin chains regulate metabolic signalling.

cell biology↗