Bcl-2 overexpression, commonly seen in follicular lymphoma due to t(14;18), promotes tumour cell survival by:

• A Directly activating caspase-9 in the intrinsic apoptotic pathway
• B Upregulating extrinsic apoptosis via death receptor signalling
• C Sequestering pro-apoptotic proteins (Bax, Bak) and preventing cytochrome c release from mitochondria ✓
• D Inhibiting p53 transcription of apoptotic target genes

Explanation

Bcl-2 is an anti-apoptotic protein of the Bcl-2 family that resides on the outer mitochondrial membrane. It functions by heterodimerising with and neutralising pro-apoptotic BH3-only proteins and effectors Bax and Bak, thereby preventing mitochondrial outer membrane permeabilisation (MOMP) and cytochrome c release. Without cytochrome c, the apoptosome (Apaf-1/caspase-9 complex) cannot form. Caspase-9 activation requires cytochrome c; Bcl-2 prevents this.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.