Proteomic and Metabolomic Characterization of a Mammalian Cellular Transition from Quiescence to Proliferation
Ho-Joon Lee,
Mark P. Jedrychowski,
Arunachalam Vinayagam,
Ning Wu,
Ng Shyh-Chang,
Yanhui Hu,
Chua Min-Wen,
Jodene K. Moore,
John M. Asara,
Costas A. Lyssiotis,
Norbert Perrimon,
Steven P. Gygi,
Lewis C. Cantley,
Marc W. Kirschner
Affiliations
Ho-Joon Lee
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
Mark P. Jedrychowski
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Arunachalam Vinayagam
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Ning Wu
Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, MI 49503, USA
Ng Shyh-Chang
Stem Cell & Regenerative Biology, Genome Institute of Singapore, S138672 Singapore, Singapore
Yanhui Hu
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Chua Min-Wen
Stem Cell & Regenerative Biology, Genome Institute of Singapore, S138672 Singapore, Singapore
Jodene K. Moore
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
John M. Asara
Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA
Costas A. Lyssiotis
Division of Gastroenterology, Department of Molecular and Integrative Physiology and Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Norbert Perrimon
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Steven P. Gygi
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Lewis C. Cantley
Meyer Cancer Center, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
Marc W. Kirschner
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
There exist similarities and differences in metabolism and physiology between normal proliferative cells and tumor cells. Once a cell enters the cell cycle, metabolic machinery is engaged to facilitate various processes. The kinetics and regulation of these metabolic changes have not been properly evaluated. To correlate the orchestration of these processes with the cell cycle, we analyzed the transition from quiescence to proliferation of a non-malignant murine pro-B lymphocyte cell line in response to IL-3. Using multiplex mass-spectrometry-based proteomics, we show that the transition to proliferation shares features generally attributed to cancer cells: upregulation of glycolysis, lipid metabolism, amino-acid synthesis, and nucleotide synthesis and downregulation of oxidative phosphorylation and the urea cycle. Furthermore, metabolomic profiling of this transition reveals similarities to cancer-related metabolic pathways. In particular, we find that methionine is consumed at a higher rate than that of other essential amino acids, with a potential link to maintenance of the epigenome.