Question 1

What does BCL2 do?

Accepted Answer

BCL2 is an anti-apoptotic protein that anchors in the outer mitochondrial membrane and sequesters pro-apoptotic BH3-only proteins (BIM, PUMA, BAD), preventing BAX and BAK from oligomerising and forming pores that release cytochrome c. BCL2 therefore blocks the intrinsic apoptotic pathway at the mitochondria.

Question 2

How does BCL2 cause follicular lymphoma?

Accepted Answer

The t(14;18) translocation places BCL2 under control of the immunoglobulin heavy-chain enhancer, causing massive BCL2 overexpression in B cells. This blocks normal apoptosis during B-cell development and maturation, allowing cells with additional mutations in MYC, EZH2, or CREBBP to accumulate and form lymphoma.

Question 3

How does venetoclax work?

Accepted Answer

Venetoclax (Venclexta) is a BH3-mimetic small molecule that occupies BCL2's hydrophobic groove, displacing pro-apoptotic BH3-only proteins and triggering rapid, caspase-dependent apoptosis. It produces responses within hours in some patients and is approved for CLL, AML, and multiple myeloma.

Question 4

Is BCL2 related to p53?

Accepted Answer

Yes — wild-type p53 transcriptionally represses BCL2 and activates pro-apoptotic BCL2 family members including BAX and PUMA. Loss of p53 therefore permits high BCL2 expression and resistance to apoptosis induction by chemotherapy — one reason TP53-mutant tumours are often chemoresistant.

BCL2 Gene Function

Overview

More Apoptosis Regulators