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Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase.

Publication ,  Journal Article
Lin, W-C; Chakraborty, A; Huang, S-C; Wang, P-Y; Hsieh, Y-J; Chien, K-Y; Lee, Y-H; Chang, C-C; Tang, H-Y; Lin, Y-T; Tung, C-S; Luo, J-D ...
Published in: Cell reports
September 2018

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.

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Published In

Cell reports

DOI

EISSN

2211-1247

ISSN

2211-1247

Publication Date

September 2018

Volume

24

Issue

10

Start / End Page

2733 / 2745.e7

Related Subject Headings

  • Protein Serine-Threonine Kinases
  • Protein Processing, Post-Translational
  • Methylation
  • Humans
  • Homocysteine
  • Histidine
  • Folic Acid
  • Carbon-Nitrogen Ligases
  • Animals
  • 31 Biological sciences
 

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Lin, W.-C., Chakraborty, A., Huang, S.-C., Wang, P.-Y., Hsieh, Y.-J., Chien, K.-Y., … Pai, L.-M. (2018). Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase. Cell Reports, 24(10), 2733-2745.e7. https://doi.org/10.1016/j.celrep.2018.08.007
Lin, Wei-Cheng, Archan Chakraborty, Shih-Chia Huang, Pei-Yu Wang, Ya-Ju Hsieh, Kun-Yi Chien, Yen-Hsien Lee, et al. “Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase.Cell Reports 24, no. 10 (September 2018): 2733-2745.e7. https://doi.org/10.1016/j.celrep.2018.08.007.
Lin W-C, Chakraborty A, Huang S-C, Wang P-Y, Hsieh Y-J, Chien K-Y, et al. Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase. Cell reports. 2018 Sep;24(10):2733-2745.e7.
Lin, Wei-Cheng, et al. “Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase.Cell Reports, vol. 24, no. 10, Sept. 2018, pp. 2733-2745.e7. Epmc, doi:10.1016/j.celrep.2018.08.007.
Lin W-C, Chakraborty A, Huang S-C, Wang P-Y, Hsieh Y-J, Chien K-Y, Lee Y-H, Chang C-C, Tang H-Y, Lin Y-T, Tung C-S, Luo J-D, Chen T-W, Lin T-Y, Cheng M-L, Chen Y-T, Yeh C-T, Liu J-L, Sung L-Y, Shiao M-S, Yu J-S, Chang Y-S, Pai L-M. Histidine-Dependent Protein Methylation Is Required for Compartmentalization of CTP Synthase. Cell reports. 2018 Sep;24(10):2733-2745.e7.
Journal cover image

Published In

Cell reports

DOI

EISSN

2211-1247

ISSN

2211-1247

Publication Date

September 2018

Volume

24

Issue

10

Start / End Page

2733 / 2745.e7

Related Subject Headings

  • Protein Serine-Threonine Kinases
  • Protein Processing, Post-Translational
  • Methylation
  • Humans
  • Homocysteine
  • Histidine
  • Folic Acid
  • Carbon-Nitrogen Ligases
  • Animals
  • 31 Biological sciences