Drug Target and Biomarker: BCL2L1 (BCL-XL) (G598)

Target Name: BCL2L1

NCBI ID: G598

Drug Target and Biomarker: BCL2L1 (BCL-XL)

BCL-XL is a protein that plays a role in regulating apoptosis in both normal cells and during flavivirus infection. It delays apoptosis in normal cells, allowing the virus to spread to neighboring cells and contribute to high pathogenicity. However, inhibiting BCL-XL accelerates apoptosis upon infection and inhibits viral dissemination.

BCL-XL is an isoform of Bcl-x that inhibits the activation of Bax and Bak, thus preventing the loss of mitochondrial outer membrane integrity and release of cytochrome c. Therefore, BCL-XL is considered anti-apoptotic.

Another isoform of Bcl-x, Bcl-xS, can inhibit BCL-XL and, when activated, leads to the loss of mitochondrial outer membrane integrity and subsequent apoptotic cell death.

The expression of BCL-XL is regulated by PARK2 ubiquitin E3 ligase, which controls its levels to regulate cell death.

In cancer cells, pro-survival proteins like BCL-2, BCL-XL, and MCL-1 bind to and inhibit pro-apoptotic proteins, such as BAX and BAK. However, when cells are treated with certain combinations of compounds, the pro-apoptotic proteins are released and activated, leading to efficient induction of apoptosis.

BCL-XL, along with BCL-2, is involved in B-CLL resistance to apoptosis, contributing to cell survival and resistance to cell death. The interaction between NTSR2 and TrkB receptors, strengthened by BDNF activation, triggers pro-survival pathways via phosphorylation of NTSR2 and the expression of downstream anti-apoptotic proteins, including BCL-XL. However, inhibiting NTSR2 can re-establish B-CLL apoptosis.

These findings highlight the diverse roles of BCL2L1 (BCL-XL) in regulating apoptosis, its involvement in viral pathogenicity, and its relevance in cancer and B-CLL survival.

Protein Name: BCL2 Like 1

Functions: Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis

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