Figure 6
From: Resistance to HSP90 inhibition involving loss of MCL1 addiction
Schematic representation of the HSP90 inhibition-induced apoptosis in sensitive cells and in the context of acquired resistance. In sensitive cells, HSP90 inhibition targets the BH3-only proteins BID, BIK and PUMA and the pro-survival BCL-2 family protein MCL1 (white boxes). HSP90 inhibition requires complex interplay of these proteins to mediate BAX/BAK-dependent apoptosis. In resistant cells, MCL1 repression is conserved, however, BIK is not essential. To achieve apoptosis both the activation of BID and PUMA by HSP90 inhibition, and the targeting of the pro-survival proteins BCL-xL and BCL-w by ABT737, are needed.
