mTOR dual inhibitors induce apoptosis in ALL cells through 2 distinct pathways controlled by the 2 mTOR complexes, mTORC1 and mTORC2. mTORC1 inhibition reduces activity of EIF4E and expression of c-MYC, leading to increased expression of the proapoptotic protein PUMA. mTORC2 inhibition increases expression of EGR1 that activates transcription of the proapoptotic protein BIM. The expression of EGR1 depends in part on NF-κB activity which might be suppressed by mTORC2. The figure has been adapted from Figure 7H in the article by Yun et al that begins on page 2711.

mTOR dual inhibitors induce apoptosis in ALL cells through 2 distinct pathways controlled by the 2 mTOR complexes, mTORC1 and mTORC2. mTORC1 inhibition reduces activity of EIF4E and expression of c-MYC, leading to increased expression of the proapoptotic protein PUMA. mTORC2 inhibition increases expression of EGR1 that activates transcription of the proapoptotic protein BIM. The expression of EGR1 depends in part on NF-κB activity which might be suppressed by mTORC2. The figure has been adapted from Figure 7H in the article by Yun et al that begins on page 2711.

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