A model for dual inhibition of BCL2 and MCL1 to release BIM and induce apoptosis. A model for dual inhibition of BCL2 and MCL1 to release BIM and induce.

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A model for dual inhibition of BCL2 and MCL1 to release BIM and induce apoptosis. A model for dual inhibition of BCL2 and MCL1 to release BIM and induce apoptosis. BCL2 protein function can be inhibited by either venetoclax or S55746, releasing BIM from binding to BCL2. BIM is subsequently sequestered by MCL1. BIM is released from MCL1 by NOXA, through genetic amplification or pharmacologic induction by the HDAC inhibitor panobinostat. The free BIM can directly activate BAX/BAK and induce cell death. Yuxuan Liu et al. PNAS 2018;115:47:12034-12039 ©2018 by National Academy of Sciences