Journal article
Mapping Post-Translational Modifications of de Novo Purine Biosynthetic Enzymes: Implications for Pathway Regulation
Journal of proteome research, Vol.18(5), pp.2078-2087
05/03/2019
DOI: 10.1021/acs.jproteome.8b00969
PMCID: PMC6499638
PMID: 30964683
Abstract
Purines represent a class of essential metabolites produced by the cell to maintain cellular homeostasis and facilitate cell proliferation. In times of high purine demand, the de novo purine biosynthetic pathway is activated; however, the mechanisms that facilitate this process are largely unknown. One plausible mechanism is through intracellular signaling, which results in enzymes within the pathway becoming post-translationally modified to enhance their individual enzyme activities and the overall pathway metabolic flux. Here, we employ a proteomic strategy to investigate the extent to which de novo purine biosynthetic pathway enzymes are post-translationally modified in 293T cells. We identified 7 post-translational modifications on 135 residues across the 6 human pathway enzymes. We further asked whether there were differences in the post-translational modification state of each pathway enzyme isolated from cells cultured in the presence or absence of purines. Of the 174 assigned modifications, 67% of them were only detected in one experimental growth condition in which a significant number of serine and threonine phosphorylations were noted. A survey of the most-probable kinases responsible for these phosphorylation events uncovered a likely AKT phosphorylation site at residue Thr397 of PPAT, which was only detected in cells under purine-supplemented growth conditions. These data suggest that this modification might alter enzyme activity or modulate its interaction(s) with downstream pathway enzymes. Together, these findings propose a role for post-translational modifications in pathway regulation and activation to meet intracellular purine demand.
Details
- Title: Subtitle
- Mapping Post-Translational Modifications of de Novo Purine Biosynthetic Enzymes: Implications for Pathway Regulation
- Creators
- Chunliang Liu - Pennsylvania State UniversityGiselle M. Knudsen - University of California, San FranciscoAnthony M. Pedley - Pennsylvania State UniversityJingxuan He - Pennsylvania State UniversityJared L. Johnson - Cornell UniversityTomer M. Yaron - Cornell UniversityLewis C. Cantley - Beth Israel Deaconess Medical CenterStephen J. Benkovic - Pennsylvania State University
- Resource Type
- Journal article
- Publication Details
- Journal of proteome research, Vol.18(5), pp.2078-2087
- DOI
- 10.1021/acs.jproteome.8b00969
- PMID
- 30964683
- PMCID
- PMC6499638
- NLM abbreviation
- J Proteome Res
- ISSN
- 1535-3893
- eISSN
- 1535-3907
- Publisher
- Amer Chemical Soc
- Number of pages
- 10
- Grant note
- R01GM024129; P41GM103481; IL35CA197588 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM024129 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) Adelson Family Foundation R35CA197588 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 05/03/2019
- Academic Unit
- Biochemistry and Molecular Biology
- Record Identifier
- 9984771646502771
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