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Molecular and Cellular Biology, August 2002, p. 5793-5800, Vol. 22, No. 16
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.16.5793-5800.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

A Functional Screen for Myc-Responsive Genes Reveals Serine Hydroxymethyltransferase, a Major Source of the One-Carbon Unit for Cell Metabolism

Mikhail A. Nikiforov,1 Sanjay Chandriani,1 Brenda O'Connell,2 Oleksi Petrenko,1 Iulia Kotenko,1 Andrew Beavis,1 John M. Sedivy,2 and Michael D. Cole1*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544,1 Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 029122

Received 21 November 2001/ Returned for modification 22 January 2002/ Accepted 7 May 2002

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.

* Corresponding author. Mailing address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544. Phone: (609) 258-5936. Fax: (609) 258-4575. E-mail: mcole{at}molbio.princeton.edu.

Molecular and Cellular Biology, August 2002, p. 5793-5800, Vol. 22, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.16.5793-5800.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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