Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase
2018-09-04
发表期刊CELL REPORTS (IF:7.5[JCR-2023],8.5[5-Year])
ISSN2211-1247
卷号24期号:10页码:2733-+
发表状态已发表
DOI10.1016/j.celrep.2018.08.007
摘要

CTP synthase (CTPS) forms compartmentalized filaments in response to substrate availability and environmental nutrient status. However, the physiological role of filaments and mechanisms for filament assembly are not well understood. Here, we provide evidence that CTPS forms filaments in response to histidine influx during glutamine starvation. Tetramer conformation-based filament formation restricts CTPS enzymatic activity during nutrient deprivation. CTPS protein levels remain stable in the presence of histidine during nutrient deprivation, followed by rapid cell growth after stress relief. We demonstrate that filament formation is controlled by methylation and that histidine promotes re-methylation of homocysteine by donating one-carbon intermediates to the cytosolic folate cycle. Furthermore, we find that starvation stress and glutamine deficiency activate the GCN2/ATF4/MTHFD2 axis, which coordinates CTPS filament formation. CTPS filament formation induced by histidine-mediated methylation may be a strategy used by cancer cells to maintain homeostasis and ensure a growth advantage in adverse environments.

收录类别SCI ; SCIE
资助项目Ministry of Education (MOE), Taiwan[EMRPD1G0041]
WOS研究方向Cell Biology
WOS类目Cell Biology
WOS记录号WOS:000443588800020
出版者CELL PRESS
WOS关键词SYNTHETASE-ACTIVITY ; CANCER-CELLS ; FILAMENT FORMATION ; LIVING CELLS ; DROSOPHILA ; ACID ; INHIBITION ; QUANTIFICATION ; METABOLOME ; DEFICIENCY
原始文献类型Article
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文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/27698
专题生命科学与技术学院
生命科学与技术学院_PI研究组_刘冀珑组
通讯作者Pai, Li-Mei
作者单位
1.Chang Gung Univ, Grad Inst Biomed Sci, Coll Med, Taoyuan 33302, Taiwan
2.Chang Gung Univ, Dept Biochem & Mol Biol, Coll Med, Taoyuan 33302, Taiwan
3.Chang Gung Univ, Dept Biomed Sci, Coll Med, Taoyuan 33302, Taiwan
4.Chang Gung Univ, Mol Med Res Ctr, Taoyuan 33302, Taiwan
5.Chang Gung Univ, Hlth Aging Res Ctr, Taoyuan 33302, Taiwan
6.Chang Gung Univ, Bioinformat Core Lab, Taoyuan 33302, Taiwan
7.Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan
8.Acad Sinica, Inst Cellular & Organism Biol, Taipei 11529, Taiwan
9.Acad Sinica, Agr Biotechnol Res Ctr, Taipei 11529, Taiwan
10.Natl Taiwan Univ, Inst Biotechnol, Taipei 106, Taiwan
11.Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM 87545 USA
12.Natl Def Med Ctr, Grad Inst Life Sci, Taipei 114, Taiwan
13.Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3PT, England
14.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
15.Chang Gung Mem Hosp, Dept Otolaryngol Head Surg, Linkou, Taiwan
16.Chang Gung Mem Hosp, Dept Neck Surg, Linkou, Taiwan
17.Chang Gung Mem Hosp, Liver Res Ctr, Linkou, Taiwan
18.Chang Gung Mem Hosp, Clin Metabol Core Lab, Linkou, Taiwan
19.Chang Gung Mem Hosp, Clin Prote Core Lab, Linkou, Taiwan
20.Chang Gung Mem Hosp, Dept Nephrol, Kidney Res Ctr, Linkou, Taiwan
推荐引用方式
GB/T 7714
Lin, Wei-Cheng,Chakraborty, Archan,Huang, Shih-Chia,et al. Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase[J]. CELL REPORTS,2018,24(10):2733-+.
APA Lin, Wei-Cheng.,Chakraborty, Archan.,Huang, Shih-Chia.,Wang, Pei-Yu.,Hsieh, Ya-Ju.,...&Pai, Li-Mei.(2018).Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase.CELL REPORTS,24(10),2733-+.
MLA Lin, Wei-Cheng,et al."Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase".CELL REPORTS 24.10(2018):2733-+.
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