Role of activating transcription factor 4 in the hepatic response to amino acid depletion by asparaginase.

ABSTRACT: The anti-leukemic agent asparaginase activates the integrated stress response (ISR) kinase GCN2 and inhibits signaling via mechanistic target of rapamycin complex 1 (mTORC1). The study objective was to investigate the protective role of activating transcription factor 4 (ATF4) in controlling the hepatic transcriptome and mediating GCN2-mTORC1 signaling during asparaginase. We compared global gene expression patterns in livers from wildtype, Gcn2 ^-/-, and Atf4 ^-/- mice treated with asparaginase or excipient and further explored selected responses in livers from Atf4 ^+/- mice. Here, we show that ATF4 controls a hepatic gene expression profile that overlaps with GCN2 but is not required for downregulation of mTORC1 during asparaginase. Ingenuity pathway analys

SUBMITTER: Al-Baghdadi RJT 

PROVIDER: S-EPMC5430736 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature