BCL2L11 - BCL2 like 11 | Elisa - Clia - Antibody - Protein

Background

BCL2-like 11 (BCL2L11), also known as BIM (Bcl-2-interacting mediator of cell death), is a pro-apoptotic member of the BCL-2 protein family. It plays a pivotal role in the intrinsic pathway of apoptosis, primarily involved in regulating cell death in response to various cellular stress signals. BCL2L11 is essential in maintaining cellular homeostasis by eliminating damaged or unwanted cells, thus preventing the development of diseases such as cancer. This protein is highly conserved among species, indicating its critical function in cellular processes. Dysregulation of BCL2L11 expression or function can lead to aberrant cell survival, contributing to the pathogenesis of various diseases.

Protein Structure

• General Features: BCL2L11 is characterized by the presence of the BCL-2 homology (BH) domains, which are crucial for its pro-apoptotic activity.
• BH3 Domain: This domain is essential for the interaction with anti-apoptotic BCL-2 family members, promoting apoptosis.
• Other Domains: BCL2L11 also contains other BH domains (BH1, BH2, and BH4) that facilitate its interaction with other proteins and enhance its apoptotic functions.
• Isoforms: BCL2L11 exists in multiple isoforms generated by alternative splicing, including BIM_EL, BIM_L, and BIM_S, which differ in their pro-apoptotic potency and regulatory mechanisms.

Classification and Subtypes

BCL2L11 belongs to the BH3-only subgroup of the BCL-2 family:

• BH3-Only Proteins: This subgroup includes other pro-apoptotic proteins like BAD, BID, and PUMA, which share the BH3 domain and play roles in apoptosis regulation.
• Isoforms of BCL2L11: The three major isoforms—BIM_EL (extra long), BIM_L (long), and BIM_S (short)—differ in their apoptotic activity and regulatory pathways.

Function and Biological Significance

• Apoptosis Regulation: BCL2L11 initiates apoptosis by binding to and antagonizing anti-apoptotic BCL-2 proteins, releasing pro-apoptotic effectors like BAX and BAK to trigger mitochondrial outer membrane permeabilization (MOMP) and cytochrome c release.
• Cellular Stress Response: It responds to various stress signals, including cytokine deprivation, DNA damage, and endoplasmic reticulum stress, to induce cell death.
• Immune System Regulation: BCL2L11 is crucial in the development and homeostasis of the immune system by regulating the apoptosis of lymphocytes and other immune cells.

Clinical Issues

• Cancer: Dysregulation of BCL2L11 expression, often through gene deletion or epigenetic silencing, is implicated in the development and progression of several cancers, including leukemia, lymphoma, and solid tumors. Reduced BCL2L11 levels contribute to chemoresistance and poor prognosis in cancer patients.
• Autoimmune Diseases: Aberrant regulation of BCL2L11 can lead to the survival of autoreactive lymphocytes, contributing to autoimmune conditions.
• Neurodegenerative Diseases: Altered BCL2L11 activity has been associated with neurodegenerative disorders, where inappropriate apoptosis leads to neuronal loss.

Summary

BCL2-like 11 (BCL2L11) is a critical pro-apoptotic protein involved in the regulation of cell death through the intrinsic apoptotic pathway. It interacts with anti-apoptotic BCL-2 family members to promote apoptosis in response to cellular stress. The protein exists in multiple isoforms with varying apoptotic potentials. Dysregulation of BCL2L11 is associated with various clinical conditions, including cancer, autoimmune diseases, and neurodegenerative disorders. Understanding the molecular mechanisms governing BCL2L11 function and regulation provides insights into therapeutic strategies for these diseases.