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

Research output: Contribution to journalArticle

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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

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Guanidinoacetate N-Methyltransferase
Creatine
Apoptosis
Food
Fatty Acids
Tumor Suppressor Protein p53
Glucose
p53 Genes
Starvation
DNA Damage
Decision Making
Up-Regulation
Adenosine Triphosphate
Enzymes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

GAMT, a p53-Inducible Modulator of Apoptosis, Is Critical for the Adaptive Response to Nutrient Stress. / Ide, Takao; Brown-Endres, Lauren; Chu, Kiki; Ongusaha, Pat P.; Ohtsuka, Takao; El-Deiry, Wafik S.; Aaronson, Stuart A.; Lee, Sam W.

In: Molecular Cell, Vol. 36, No. 3, 13.11.2009, p. 379-392.

Research output: Contribution to journalArticle

Ide, T, Brown-Endres, L, Chu, K, Ongusaha, PP, Ohtsuka, T, El-Deiry, WS, Aaronson, SA & Lee, SW 2009, 'GAMT, a p53-Inducible Modulator of Apoptosis, Is Critical for the Adaptive Response to Nutrient Stress', Molecular Cell, vol. 36, no. 3, pp. 379-392. https://doi.org/10.1016/j.molcel.2009.09.031
Ide, Takao ; Brown-Endres, Lauren ; Chu, Kiki ; Ongusaha, Pat P. ; Ohtsuka, Takao ; El-Deiry, Wafik S. ; Aaronson, Stuart A. ; Lee, Sam W. / GAMT, a p53-Inducible Modulator of Apoptosis, Is Critical for the Adaptive Response to Nutrient Stress. In: Molecular Cell. 2009 ; Vol. 36, No. 3. pp. 379-392.
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