BCL2L1 - BCL2 like 1 | Elisa - Clia - Antibody - Protein

Background

BCL2L1, also known as BCL-XL (B-cell lymphoma-extra large), is a member of the BCL2 protein family that plays a crucial role in regulating apoptosis. BCL2L1 was identified due to its homology with the BCL2 gene and is located on chromosome 20q11.21. This gene produces two main isoforms through alternative splicing: BCL-XL, which is anti-apoptotic, and BCL-XS, which is pro-apoptotic. BCL-XL is widely expressed in various tissues, including the hematopoietic system, nervous system, and epithelial tissues, indicating its importance in cell survival and homeostasis.

Protein Structure

The structure of BCL2L1 is characterized by the presence of four BCL2 homology (BH) domains:

• BH1, BH2, and BH3 Domains: These domains are involved in the formation of hetero- and homodimers with other BCL2 family members, critical for its anti-apoptotic function.
• BH4 Domain: Located at the N-terminus, this domain is essential for the anti-apoptotic activity of BCL-XL.
• Transmembrane (TM) Domain: This C-terminal domain helps anchor BCL-XL to the mitochondrial outer membrane, where it exerts its function by maintaining mitochondrial integrity.

Classification and Subtypes

BCL2L1 belongs to the BCL2 protein family, which includes:

1. Anti-apoptotic Proteins: Such as BCL2, BCL-XL, and MCL1, which inhibit apoptosis and promote cell survival.
2. Pro-apoptotic Effector Proteins: Including BAX and BAK, which promote apoptosis by permeabilizing the mitochondrial membrane.
3. Pro-apoptotic BH3-only Proteins: Such as BID, BIM, and PUMA, which regulate the activity of anti-apoptotic and effector proteins.

Function and Biological Significance

BCL2L1 (BCL-XL) primarily functions to inhibit apoptosis, thus promoting cell survival under various stress conditions:

• Inhibition of Pro-apoptotic Proteins: BCL-XL binds to and neutralizes pro-apoptotic proteins like BAX and BAK, preventing them from inducing mitochondrial membrane permeabilization.
• Mitochondrial Integrity: By preserving mitochondrial membrane integrity, BCL-XL prevents the release of apoptogenic factors such as cytochrome c, thereby inhibiting the activation of the caspase cascade.
• Cell Survival: BCL-XL plays a crucial role in the survival of various cell types, particularly in the nervous system, immune system, and during development.

Clinical Issues

Dysregulation of BCL2L1 has significant implications in various diseases:

• Cancer: Overexpression of BCL-XL is commonly observed in numerous cancers, including lymphomas, leukemias, and solid tumors. This overexpression contributes to chemotherapy resistance by inhibiting apoptosis in cancer cells.
• Neurodegenerative Diseases: Altered expression of BCL-XL is linked to neurodegenerative conditions such as Alzheimer's and Parkinson's disease, where it can either protect neurons from apoptosis or contribute to neurodegeneration under certain pathological conditions.
• Cardiovascular Diseases: BCL-XL is also involved in protecting cardiac cells from apoptosis during ischemic injury, indicating its role in cardiovascular health.

Summary

BCL2L1 (BCL-XL) is a vital regulator of apoptosis, essential for maintaining cellular homeostasis and promoting cell survival under stress. It inhibits pro-apoptotic proteins, preserves mitochondrial integrity, and plays a critical role in various physiological processes. Dysregulation of BCL2L1 is associated with multiple diseases, particularly cancers and neurodegenerative disorders, making it a potential therapeutic target for developing treatments for these conditions. Understanding the function and regulation of BCL2L1 is crucial for advancing therapeutic strategies in oncology and neurobiology.