Year published: 2022

Impaired degradation of YAP1 and IL6ST by chaperone-mediated autophagy promotes proliferation and migration of normal and hepatocellular carcinoma cells

Impaired degradation of the transcriptional coactivator YAP1 and IL6ST (interleukin 6 cytokine familysignal transducer), two proteins deregulated in liver cancer, has been shown to promote tumorgrowth. Here, we demonstrate that YAP1 and IL6ST are novel substrates of chaperone-mediatedautophagy (CMA) in human hepatocellular carcinoma (HCC) and hepatocyte cell lines. Knockdown ofthe lysosomal CMA receptor LAMP2A increases …

Impaired degradation of YAP1 and IL6ST by chaperone-mediated autophagy promotes proliferation and migration of normal and hepatocellular carcinoma cells Read More »

Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation

3-phosphoinositide-dependent kinase 1 (PDK1) is an essential serine/threonine protein kinase, which plays a crucial role in cell growth and proliferation. It is often referred to as a ‘master’ kinase due to its ability to activate at least 23 downstream protein kinases implicated in various signaling pathways. In this study, we have elucidated the mechanism of …

Activation of the essential kinase PDK1 by phosphoinositide-driven trans-autophosphorylation Read More »

NMD is required for timely cell fate transitions by fine-tuning gene expression and regulating translation

Cell fate transitions depend on balanced rewiring of transcription and translation programs to mediate ordered developmental progression. Components of the nonsense-mediated mRNA decay (NMD) pathway have been implicated in regulating embryonic stem cell (ESC) differentiation, but the exact mechanism is unclear. Here we show that NMD controls expression levels of the translation initiation factor Eif4a2 …

NMD is required for timely cell fate transitions by fine-tuning gene expression and regulating translation Read More »

Nonredundancy of IL-1α and IL-1β is defined by distinct regulation of tissues orchestrating resistance versus tolerance to infection

Interleukin-1α (IL-1α) and IL-1β are inflammatory cytokines with important roles in health and disease. They trigger the same receptor and elicit comparable cellular responses but, for poorly understood reasons, are not redundant in vivo. Here, we decoupled IL-1α and IL-1β functions that drive protective responses against invasive infection with group A Streptococcus. IL-1β was essential …

Nonredundancy of IL-1α and IL-1β is defined by distinct regulation of tissues orchestrating resistance versus tolerance to infection Read More »

Network cartographs for interpretable visualizations

Networks offer an intuitive visual representation of complex systems. Important network characteristics can often be recognized by eye and, in turn, patterns that stand out visually often have a meaningful interpretation. In conventional network layout algorithms, however, the precise determinants of a node’s position within a layout are difficult to decipher and to control. Here …

Network cartographs for interpretable visualizations Read More »

Interferons reshape the 3D conformation and accessibility of macrophage chromatin

Engagement of macrophages in innate immune responses is directed by type I and type II interferons (IFN-I and IFN-γ, respectively). IFN triggers drastic changes in cellular transcriptomes, executed by JAK-STAT signal transduction and the transcriptional control of interferon-stimulated genes (ISG) by STAT transcription factors. Here, we study the immediate-early nuclear response to IFN-I and IFN-γ …

Interferons reshape the 3D conformation and accessibility of macrophage chromatin Read More »