A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism.
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.
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Mikhail A
MA
Nikiforov
Sanjay
S
Chandriani
Brenda
B
O'Connell
Oleksi
O
Petrenko
Iulia
I
Kotenko
Andrew
A
Beavis
John M
JM
Sedivy
Michael D
MD
Cole
D000818:Animals; D002244:Carbon / Q000378:metabolism*; D002468:Cell Physiological Phenomena; D002469:Cell Separation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000502:physiology; D005434:Flow Cytometry; D015723:Gene Library; D016259:Genes, myc; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains
D016271:Proto-Oncogene Proteins c-myc; D002244:Carbon; D012696:Glycine Hydroxymethyltransferase