BclxSBclxL

BclxSBclxL is a shorthand reference to the two major alternatively spliced isoforms produced by the human BCL2-like 1 gene (BCL2L1): Bcl-xL and Bcl-xS. These two proteins arise from the same gene through differential splicing and encode functionally opposite regulators of apoptosis. The BCL2L1 gene is located on chromosome 20 and generates multiple transcripts, with Bcl-xL and Bcl-xS being the most studied in mammals.

Bcl-xL is the longer, anti-apoptotic member of the Bcl-2 protein family. It localizes mainly to the outer mitochondrial membrane where it helps maintain mitochondrial integrity by inhibiting mitochondrial outer membrane permeabilization (MOMP). Bcl-xL exerts its effect by binding pro-apoptotic proteins such as Bax and Bak and by antagonizing BH3-only proteins, thereby preventing cytochrome c release and caspase activation. Because of its role in promoting cell survival, Bcl-xL is frequently expressed at high levels in healthy tissues and is often upregulated in cancers, contributing to resistance to cellular stress and chemotherapy.

Bcl-xS is the shorter, pro-apoptotic splice variant. It lacks much of the transmembrane-anchoring sequence found in Bcl-xL and contains an active BH3 domain that promotes apoptosis by antagonizing anti-apoptotic Bcl-2 family members and facilitating Bax/Bak activation. Bcl-xS levels are typically lower than Bcl-xL in many tissues but can be upregulated in response to cellular stress.

Overall, the relative expression of Bcl-xL and Bcl-xS from the BCL2L1 transcript modulates cell fate, with implications for development, physiology, and disease, particularly cancer.