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Sujin, Park
유전체 교정 연구단
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Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis

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Title
Transcription factors TEAD2 and E2A globally repress acetyl-CoA synthesis to promote tumorigenesis
Author(s)
Sujin Park; Mossmann, Dirk; Chen, Qian; Wang, Xueya; Dazert, Eva; Colombi, Marco; Schmidt, Alexander; Ryback, Brendan; Ng, Charlotte K. Y.; Terracciano, Luigi M.; Heim, Markus H.; Hall, Michael N.
Publication Date
2022-11
Journal
MOLECULAR CELL, v.82, no.22, pp.4246 - 4261
Publisher
CELL PRESS
Abstract
Acetyl-coenzyme A (acetyl-CoA) plays an important role in metabolism, gene expression, signaling, and other cellular processes via transfer of its acetyl group to proteins and metabolites. However, the synthesis and usage of acetyl-CoA in disease states such as cancer are poorly characterized. Here, we investigated global acetyl-CoA synthesis and protein acetylation in a mouse model and patient samples of hepatocellular carci-noma (HCC). Unexpectedly, we found that acetyl-CoA levels are decreased in HCC due to transcriptional downregulation of all six acetyl-CoA biosynthesis pathways. This led to hypo-acetylation specifically of non-histone proteins, including many enzymes in metabolic pathways. Importantly, repression of acetyl-CoA synthesis promoted oncogenic dedifferentiation and proliferation. Mechanistically, acetyl-CoA synthe-sis was repressed by the transcription factors TEAD2 and E2A, previously unknown to control acetyl-CoA synthesis. Knockdown of TEAD2 and E2A restored acetyl-CoA levels and inhibited tumor growth. Our find-ings causally link transcriptional reprogramming of acetyl-CoA metabolism, dedifferentiation, and cancer.
URI
https://pr.ibs.re.kr/handle/8788114/12534
DOI
10.1016/j.molcel.2022.10.027
ISSN
1097-2765
Appears in Collections:
Center for Genome Engineering(유전체 교정 연구단) > 1. Journal Papers (저널논문)
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