Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues.

• Klíčová slova
• Notch targets, Warburg effect, glycolytic shift, metabolism, tissue growth,
• MeSH
• aktivace transkripce MeSH
• biologické modely MeSH
• buněčné linie MeSH
• citrátový cyklus genetika   MeSH
• energetický metabolismus genetika   MeSH
• exprese genu MeSH
• glykolýza genetika   MeSH
• lidé MeSH
• promotorové oblasti (genetika) MeSH
• proteiny Drosophily genetika   metabolismus   MeSH
• receptory Notch genetika   metabolismus   MeSH
• regulace genové exprese * MeSH
• regulační oblasti nukleových kyselin MeSH
• reportérové geny MeSH
• represorové proteiny genetika   metabolismus   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• proteiny Drosophily MeSH
• receptory Notch MeSH
• represorové proteiny MeSH
• Su(H) protein, Drosophila MeSH Prohlížeč