作者
Simon Raffel, Mattia Falcone, Niclas Kneisel, Jenny Hansson, Wei Wang, Christoph Lutz, Lars Bullinger, Gernot Poschet, Yannic Nonnenmacher, Andrea Barnert, Carsten Bahr, Petra Zeisberger, Adriana Przybylla, Markus Sohn, Martje Tönjes, Ayelet Erez, Lital Adler, Patrizia Jensen, Claudia Scholl, Stefan Fröhling, Sibylle Cocciardi, Patrick Wuchter, Christian Thiede, Anne Flörcken, Jörg Westermann, Gerhard Ehninger, Peter Lichter, Karsten Hiller, Rüdiger Hell, Carl Herrmann, Anthony D Ho, Jeroen Krijgsveld, Bernhard Radlwimmer, Andreas Trumpp
发表日期
2017/11/16
期刊
Nature
卷号
551
期号
7680
页码范围
384-388
出版商
Nature Publishing Group UK
简介
The branched-chain amino acid (BCAA) pathway and high levels of BCAA transaminase 1 (BCAT1) have recently been associated with aggressiveness in several cancer entities,,,,,. However, the mechanistic role of BCAT1 in this process remains largely uncertain. Here, by performing high-resolution proteomic analysis of human acute myeloid leukaemia (AML) stem-cell and non-stem-cell populations, we find the BCAA pathway enriched and BCAT1 protein and transcripts overexpressed in leukaemia stem cells. We show that BCAT1, which transfers α-amino groups from BCAAs to α-ketoglutarate (αKG), is a critical regulator of intracellular αKG homeostasis. Further to its role in the tricarboxylic acid cycle, αKG is an essential cofactor for αKG-dependent dioxygenases such as Egl-9 family hypoxia inducible factor 1 (EGLN1) and the ten-eleven translocation (TET) family of DNA demethylases,,,. Knockdown of BCAT1 …
学术搜索中的文章
S Raffel, M Falcone, N Kneisel, J Hansson, W Wang… - Nature, 2017