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. 2014 Mar 26;105(5):499–505. doi: 10.1111/cas.12383

Figure 2.

Figure 2

Effector proteins of Kirsten rat-sarcoma (KRAS) and apoptosis. The BCL-2 family of proteins regulates mitochondrial-driven apoptosis in KRAS mutant cancers. The BCL-2 family consists of three subfamilies: the pro-survival members such as BCL-2 or MCL1, the pro-apoptotic BCL-2 homology domain 3 (BH3)-only proteins such as BIM and PUMA, and the pro-apoptotic BAX and BCL-2 antagonist/killer (BAK; not shown in this figure). The anti-apoptotic function of oncogenic KRAS is mediated by several effector pathways that converge on the BCL-2 family of proteins. The PI3K effector pathway suppresses pro-apoptotic protein PUMA and BAX, the RAS–RAF pathway downregulates the pro-apoptotic protein BIM, and the mTORC1 pathway regulates MCL-1. In addition, the Ral-NF-κB pathway has been implicated in the regulation of BCL-XL. Thus, KRAS suppresses cell death responses through regulation of both pro-apoptotic and anti-apoptotic BCL-2 family proteins.