A Functional Screen for Myc-Responsive Genes Reveals Serine Hydroxymethyltransferase, a Major Source of the One-Carbon Unit for Cell Metabolism
| Autor: | John M. Sedivy, Brenda C. O'Connell, Sanjay Chandriani, Andrew Beavis, Iulia Kotenko, Oleksi Petrenko, Mikhail A. Nikiforov, Michael D. Cole |
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| Rok vydání: | 2002 |
| Předmět: |
Gene isoform
Genes myc Gene Expression Cell Separation Biology Rats Mutant Strains Cell Physiological Phenomena Proto-Oncogene Proteins c-myc chemistry.chemical_compound Biosynthesis Animals Humans Promoter Regions Genetic Molecular Biology Gene Cells Cultured Gene Library Glycine Hydroxymethyltransferase cDNA library Cell Biology Fibroblasts Flow Cytometry Molecular biology Carbon Mitochondria Rats Cell biology Complementation chemistry Serine hydroxymethyltransferase Chromatin immunoprecipitation |
| Zdroj: | Molecular and Cellular Biology. 22:5793-5800 |
| ISSN: | 1098-5549 |
| Popis: | A cDNA library enriched with Myc-responsive cDNAs but depleted of myc cDNAs was used in a functional screen for growth enhancement in c-myc-null cells. A cDNA clone for mitochondrial serine hydroxymethyltransferase (mSHMT) that was capable of partial complementation of the growth defects of c-myc-null cells was identified. Expression analysis and chromatin immunoprecipitation demonstrated that mSHMT is a direct Myc target gene. Furthermore, a separate gene encoding the cytoplasmic isoform of the same enzyme is also a direct target of Myc regulation. SHMT enzymes are the major source of the one-carbon unit required for folate metabolism and for the biosynthesis of nucleotides and amino acids. Our data establish a novel functional link between Myc and the regulation of cellular metabolism. |
| Databáze: | OpenAIRE |
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