共 33 条
Oncogenic Myc Induces Expression of Glutamine Synthetase through Promoter Demethylation
被引:212
作者:

Bott, Alex J.
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h-index: 0
机构:
SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

论文数: 引用数:
h-index:
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Fan, Yongjun
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Faubert, Brandon
论文数: 0 引用数: 0
h-index: 0
机构:
McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Zhao, Lu
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Appl Math, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Li, Jinyu
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h-index: 0
机构:
SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Neidler, Sarah
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Glasgow, Inst Canc Sci, Glasgow G61 1BD, Lanark, Scotland
CRUK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Sun, Yu
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SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Jaber, Nadia
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SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Krokowski, Dawid
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h-index: 0
机构:
Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Lu, Wenyun
论文数: 0 引用数: 0
h-index: 0
机构:
Princeton Univ, Dept Chem, Princeton, NJ 08544 USA
Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Pan, Ji-An
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Powers, Scott
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Rabinowitz, Joshua
论文数: 0 引用数: 0
h-index: 0
机构: SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Hatzoglou, Maria
论文数: 0 引用数: 0
h-index: 0
机构:
Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Murphy, Daniel J.
论文数: 0 引用数: 0
h-index: 0
机构:
Univ Glasgow, Inst Canc Sci, Glasgow G61 1BD, Lanark, Scotland
CRUK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Jones, Russell
论文数: 0 引用数: 0
h-index: 0
机构:
McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Wu, Song
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Appl Math, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Girnun, Geoffrey
论文数: 0 引用数: 0
h-index: 0
机构:
SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA

Zong, Wei-Xing
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h-index: 0
机构:
SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
机构:
[1] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Dept Appl Math, Stony Brook, NY 11794 USA
[3] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA
[4] McGill Univ, Dept Physiol, Montreal, PQ H3G 1Y6, Canada
[5] Univ Glasgow, Inst Canc Sci, Glasgow G61 1BD, Lanark, Scotland
[6] CRUK Beatson Inst, Glasgow G61 1BD, Lanark, Scotland
[7] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA
[8] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA
[9] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA
[10] Natl Cheng Kung Univ, Dept Life Sci, Tainan 701, Taiwan
关键词:
DNA METHYLATION;
CELL BIOLOGY;
METABOLISM;
CANCER;
MUSCLE;
PROGRAM;
PROTEIN;
LEADS;
D O I:
10.1016/j.cmet.2015.09.025
中图分类号:
Q2 [细胞生物学];
学科分类号:
071009 ;
090102 ;
摘要:
c-Myc is known to promote glutamine usage by upregulating glutaminase (GLS), which converts glutamine to glutamate that is catabolized in the TCA cycle. Here we report that in a number of human and murine cells and cancers, Myc induces elevated expression of glutamate-ammonia ligase (GLUL), also termed glutamine synthetase (GS), which catalyzes the de novo synthesis of glutamine from glutamate and ammonia. This is through upregulation of a Myc transcriptional target thymine DNA glycosylase (TDG), which promotes active demethylation of the GS promoter and its increased expression. Elevated expression of GS promotes cell survival under glutamine limitation, while silencing of GS decreases cell proliferation and xenograft tumor growth. Upon GS overexpression, increased glutamine enhances nucleotide synthesis and amino acid transport. These results demonstrate an unexpected role of Myc in inducing glutamine synthesis and suggest a molecular connection between DNA demethylation and glutamine metabolism in Myc-driven cancers.
引用
收藏
页码:1068 / 1077
页数:10
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机构:
Univ Amsterdam, Acad Med Ctr, Ctr Liver, NL-1105 BK Amsterdam, Netherlands
Univ Amsterdam, Acad Med Ctr, Dept Anat & Embryol, NL-1105 BK Amsterdam, Netherlands Univ Amsterdam, Acad Med Ctr, Ctr Liver, NL-1105 BK Amsterdam, Netherlands

Ruijter, Jan M.
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h-index: 0
机构:
Univ Amsterdam, Acad Med Ctr, Ctr Liver, NL-1105 BK Amsterdam, Netherlands
Univ Amsterdam, Acad Med Ctr, Dept Anat & Embryol, NL-1105 BK Amsterdam, Netherlands Univ Amsterdam, Acad Med Ctr, Ctr Liver, NL-1105 BK Amsterdam, Netherlands

Deutz, Nicolaas E. P.
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机构:
Univ Maastricht, Dept Surg, NL-6200 MD Maastricht, Netherlands Univ Amsterdam, Acad Med Ctr, Ctr Liver, NL-1105 BK Amsterdam, Netherlands

Lamers, Wouter H.
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机构:
Univ Amsterdam, Acad Med Ctr, Ctr Liver, NL-1105 BK Amsterdam, Netherlands
Univ Amsterdam, Acad Med Ctr, Dept Anat & Embryol, NL-1105 BK Amsterdam, Netherlands
Univ Maastricht, Dept Anat & Embryol, NL-6200 MD Maastricht, Netherlands Univ Amsterdam, Acad Med Ctr, Ctr Liver, NL-1105 BK Amsterdam, Netherlands