Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F16%3A00458021" target="_blank" >RIV/60077344:_____/16:00458021 - isvavai.cz</a>

Alternative codes found

RIV/60076658:12310/16:43891015 RIV/00216224:14740/16:00093886

Result on the web

<a href="http://rsob.royalsocietypublishing.org/content/royopenbio/6/2/150155.full.pdf" target="_blank" >http://rsob.royalsocietypublishing.org/content/royopenbio/6/2/150155.full.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1098/rsob.150155" target="_blank" >10.1098/rsob.150155</a>

Result language

angličtina

Original language name

Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle

Original language description

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 mediatingncellular 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.n

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Open Biology

ISSN

2046-2441

e-ISSN

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Volume of the periodical

6

Issue of the periodical within the volume

Feb 15

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

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UT code for WoS article

000371256100004

EID of the result in the Scopus database

2-s2.0-84962262232