GAMT, a p53-Inducible Modulator of Apoptosis, Is Critical for the Adaptive Response to Nutrient Stress

Takao Ide, Lauren Brown-Endres, Kiki Chu, Pat P. Ongusaha, Takao Ohtsuka, Wafik S. El-Deiry, Stuart A. Aaronson, Sam W. Lee

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69 Citations (Scopus)

Abstract

The p53 tumor suppressor protein has a well-established role in cell-fate decision-making processes. However, recent discoveries indicate that p53 has a non-tumor-suppressive role. Here we identify guanidinoacetate methyltransferase (GAMT), an enzyme involved in creatine synthesis, as a p53 target gene and a key downstream effector of adaptive response to nutrient stress. We show that GAMT is not only involved in p53-dependent apoptosis in response to genotoxic stress but is important for apoptosis induced by glucose deprivation. Additionally, p53→GAMT upregulates fatty acid oxidation (FAO) induced by glucose starvation, utilizing this pathway as an alternate ATP-generating energy source. These results highlight that p53-dependent regulation of GAMT allows cells to maintain energy levels sufficient to undergo apoptosis or survival under conditions of nutrient stress. The p53→GAMT pathway represents a new link between cellular stress responses and processes of creatine synthesis and FAO, demonstrating a further role of p53 in cellular metabolism.

Original languageEnglish
Pages (from-to)379-392
Number of pages14
JournalMolecular Cell
Volume36
Issue number3
DOIs
Publication statusPublished - Nov 13 2009

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Ide, T., Brown-Endres, L., Chu, K., Ongusaha, P. P., Ohtsuka, T., El-Deiry, W. S., Aaronson, S. A., & Lee, S. W. (2009). GAMT, a p53-Inducible Modulator of Apoptosis, Is Critical for the Adaptive Response to Nutrient Stress. Molecular Cell, 36(3), 379-392. https://doi.org/10.1016/j.molcel.2009.09.031