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GAMT, a p53‐Inducible Modulator of Apoptosis, Is Critical for the Adaptive Response to Nutrient Stress
Author(s) -
Chu Kiki,
Ide Takao,
BrownEndres Lauren,
Lee Sam W
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.485.4
Subject(s) - apoptosis , effector , microbiology and biotechnology , integrated stress response , chemistry , nutrient sensing , biochemistry , biology , signal transduction , translation (biology) , gene , messenger rna
The p53 tumor suppressor protein has a well‐established role in cell fate decision‐making processes through many mechanisms. However, recent discoveries indicate that p53 has much broader cellular functions that are non‐tumor‐suppressive roles, such as regulating glucose metabolism and mitochondrial respiration. Here, we identify GAMT (guanidinoacetate methyltransferase), an enzyme involved in creatine synthesis, as a novel 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 up‐regulates 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. 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.