| SLANINOVA, Vera, Michaela KRAFČÍKOVÁ, Raquel PEREZ-GOMEZ, Pavel STEFFAL, Lukáš TRANTÍREK, Sarah J. BRAY and Alena KREJCI. Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle. OPEN BIOLOGY. LONDON: ROYAL SOC, 2016, vol. 6, No 2, p. nestránkováno, 14 pp. ISSN 2046-2441. Available from: https://dx.doi.org/10.1098/rsob.150155. |
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@article{1375509,
author = {Slaninova, Vera and Krafčíková, Michaela and PerezandGomez, Raquel and Steffal, Pavel and Trantírek, Lukáš and Bray, Sarah J. and Krejci, Alena},
article_location = {LONDON},
article_number = {2},
doi = {http://dx.doi.org/10.1098/rsob.150155},
keywords = {metabolism; Notch targets; Warburg effect; glycolytic shift; tissue growth},
language = {eng},
issn = {2046-2441},
journal = {OPEN BIOLOGY},
title = {Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle},
url = {http://rsob.royalsocietypublishing.org/content/6/2/150155},
volume = {6},
year = {2016}
}
TY - JOUR
ID - 1375509
AU - Slaninova, Vera - Krafčíková, Michaela - Perez-Gomez, Raquel - Steffal, Pavel - Trantírek, Lukáš - Bray, Sarah J. - Krejci, Alena
PY - 2016
TI - Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle
JF - OPEN BIOLOGY
VL - 6
IS - 2
SP - nestránkováno
EP - nestránkováno
PB - ROYAL SOC
SN - 20462441
KW - metabolism
KW - Notch targets
KW - Warburg effect
KW - glycolytic shift
KW - tissue growth
UR - http://rsob.royalsocietypublishing.org/content/6/2/150155
L2 - http://rsob.royalsocietypublishing.org/content/6/2/150155
N2 - 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.
ER -
SLANINOVA, Vera, Michaela KRAFČÍKOVÁ, Raquel PEREZ-GOMEZ, Pavel STEFFAL, Lukáš TRANTÍREK, Sarah J. BRAY and Alena KREJCI. Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle. \textit{OPEN BIOLOGY}. LONDON: ROYAL SOC, 2016, vol.~6, No~2, p.~nestránkováno, 14 pp. ISSN~2046-2441. Available from: https://dx.doi.org/10.1098/rsob.150155.
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