Počet záznamů: 1
Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle
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SYSNO ASEP 0458021 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle Tvůrce(i) Slaninová, Věra (BC-A)
Krafčíková, M. (CZ)
Perez-Gomez, R. (CZ)
Steffal, P. (CZ)
Trantírek, L. (CZ)
Bray, S. J. (GB)
Krejčí, Alena (BC-A) RID, ORCIDCelkový počet autorů 7 Zdroj.dok. Open Biology. - : Royal Society Publishing
Roč. 6, Feb 15 (2016), s. 150155Poč.str. 14 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova metabolism ; Notch targets ; Warburg effect Vědní obor RIV EB - Genetika a molekulární biologie CEP GAP305/11/0126 GA ČR - Grantová agentura ČR GA14-08583S GA ČR - Grantová agentura ČR Institucionální podpora BC-A - RVO:60077344 UT WOS 000371256100004 EID SCOPUS 84962262232 DOI 10.1098/rsob.150155 Anotace 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.
Pracoviště Biologické centrum (od r. 2006) Kontakt Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Rok sběru 2017 Elektronická adresa http://rsob.royalsocietypublishing.org/content/royopenbio/6/2/150155.full.pdf
Počet záznamů: 1