ArticleNature structural & molecular biology2010
A metazoan ortholog of SpoT hydrolyzes ppGpp and functions in starvation responses.
Article in Nature structural & molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed.
- MESH1 functions as a metazoan PAPS phosphatase to regulate sulfation.Nature chemical biology · 2026Article
- MESH1-mediated coenzyme A degradation drives ferroptosis sensitivity and muscle pathology.The Journal of clinical investigation · 2026Article
- Identification of 4,5,6,7-Tetrabromo-1bioRxiv : the preprint server for biology · 2026Article
- Starvation-independent alarmone production inhibits translation through GTP depletion.bioRxiv : the preprint server for biology · 2026Article
- Article
- The Metazoan SpoT Homolog 1 promotes ferroptosis by regulating the intracellular redox cycle and iron levels in hepatocellular carcinoma.International journal of clinical oncology · 2025Article
- Gene Expression Depends on the Interplay Among Growth, Resource Biogenesis, and Nutrient Quality.ACS synthetic biology · 2025Article
- How to quantify magic spots - a brief overview of (p)ppGpp detection and quantitation methods.Frontiers in molecular biosciences · 2025Review
- Genome-wide changes of protein translation levels for cell and organelle proliferation in a simple unicellular alga.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Article
- Overactive mitochondrial DNA replication disrupts perinatal cardiac maturation.Nature communications · 2024Article
- Homeostatic regulation of NAD(H) and NADP(H) in cells.Genes & diseases · 2024Review
- The immune response to RNA suppresses nucleic acid synthesis by limiting ribose 5-phosphate.The EMBO journal · 2024Article
- Synthetase and Hydrolase Specificity Collectively Excludes 2'-Deoxyguanosine from Bacterial Alarmone.bioRxiv : the preprint server for biology · 2024Article
- Crosstalk between (p)ppGpp and other nucleotide second messengers.Current opinion in microbiology · 2023Review
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- Article
- Functional Characterization of Small Alarmone Synthetase and Small Alarmone Hydrolase Proteins from Treponema denticola.Microbiology spectrum · 2023Article
- Bacterial Pathogen Infection Triggers Magic Spot Nucleotide Signaling inJournal of the American Chemical Society · 2023Article
- Sound the (Smaller) Alarm: The Triphosphate Magic Spot Nucleotide pGpp.Infection and immunity · 2023Review
- Identification of a broadly conserved family of enzymes that hydrolyze (p)ppApp.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In nutrient-starved bacteria, RelA and SpoT proteins have key roles in reducing cell growth and overcoming stresses. Here we identify functional SpoT orthologs in metazoa (named Mesh1, encoded by HDDC3 in human and Q9VAM9 in Drosophila melanogaster) and reveal their structures and functions. Like the bacterial enzyme, Mesh1 proteins contain an active site for ppGpp hydrolysis and a conserved His-Asp-box motif for Mn(2+) binding. Consistent with these structural data, Mesh1 efficiently catalyzes hydrolysis of guanosine 3',5'-diphosphate (ppGpp) both in vitro and in vivo. Mesh1 also suppresses SpoT-deficient lethality and RelA-induced delayed cell growth in bacteria. Notably, deletion of Mesh1 (Q9VAM9) in Drosophila induces retarded body growth and impaired starvation resistance. Microarray analyses reveal that the amino acid-starved Mesh1 null mutant has highly downregulated DNA and protein synthesis-related genes and upregulated stress-responsible genes. These data suggest that metazoan SpoT orthologs have an evolutionarily conserved function in starvation responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.