Gene interactions and pathways from curated databases and text-mining
Blood 2011, PMID: 21715304

BCR-ABL suppresses autophagy through ATF5-mediated regulation of mTOR transcription.

Sheng, Zhi; Ma, Leyuan; Sun, Jiaoyuan E; Zhu, Lihua J; Green, Michael R

The oncoprotein BCR-ABL transforms myeloid progenitor cells and is responsible for the development of chronic myeloid leukemia (CML). In transformed cells, BCR-ABL suppresses apoptosis as well as autophagy, a catabolic process in which cellular components are degraded by the lysosomal machinery. The mechanism by which BCR-ABL suppresses autophagy is not known. Here we report that in both mouse and human BCR-ABL-transformed cells, activating transcription factor 5 (ATF5), a prosurvival factor, suppresses autophagy but does not affect apoptosis. We find that BCR-ABL, through PI3K/AKT/FOXO4 signaling, transcriptionally up-regulates ATF5 expression and that ATF5, in turn, stimulates transcription of mammalian target of rapamycin (mTOR; also called mechanistic target of rapamycin), a well-established master negative-regulator of autophagy. Previous studies have shown that the BCR-ABL inhibitor imatinib mesylate induces both apoptosis and autophagy, and that the resultant autophagy modulates the efficiency by which imatinib kills BCR-ABL-transformed cells. We demonstrate that imatinib-induced autophagy is because of inhibition of the BCR-ABL/PI3K/AKT/FOXO4/ATF5/mTOR pathway that we have identified in this study.

Diseases/Pathways annotated by Medline MESH: Cell Transformation, Neoplastic, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
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Text Mining Data

mTOR ⊣ ATF5: " BCR-ABL suppresses autophagy through ATF5 mediated regulation of mTOR transcription "

mammalian target of rapamycin → BCR-ABL: " We find that BCR-ABL , through PI3K/AKT/FOXO4 signaling, transcriptionally up-regulates ATF5 expression and that ATF5, in turn, stimulates transcription of mammalian target of rapamycin ( mTOR ; also called mechanistic target of rapamycin ), a well established master negative-regulator of autophagy "

mammalian target of rapamycin → BCR-ABL: " We find that BCR-ABL , through PI3K/AKT/FOXO4 signaling, transcriptionally up-regulates ATF5 expression and that ATF5, in turn, stimulates transcription of mammalian target of rapamycin ( mTOR ; also called mechanistic target of rapamycin ), a well established master negative-regulator of autophagy "

mammalian target of rapamycin → ATF5: " We find that BCR-ABL, through PI3K/AKT/FOXO4 signaling, transcriptionally up-regulates ATF5 expression and that ATF5 , in turn, stimulates transcription of mammalian target of rapamycin ( mTOR ; also called mechanistic target of rapamycin ), a well established master negative-regulator of autophagy "

Manually curated Databases

No curated data.