BCL2L2 - BCL2 like 2 | Elisa - Clia - Antibody - Protein

Background

BCL2-like 2 (BCL2L2), also known as BCL-W, is a member of the BCL-2 family of proteins that are pivotal regulators of apoptosis. The BCL2L2 gene is located on chromosome 14q11.2 and encodes a protein that plays a crucial role in promoting cell survival by inhibiting apoptosis. BCL2L2 is involved in various physiological processes and has significant implications in the development and progression of cancer. Its expression is tightly regulated in normal tissues, but aberrant expression is often associated with malignancies.

Protein Structure

BCL2L2 shares a similar structure with other BCL-2 family members, characterized by several BCL-2 homology (BH) domains.

• BH Domains: BCL2L2 contains four BH domains (BH1, BH2, BH3, and BH4). These domains are crucial for its function and interactions with other proteins.
• Transmembrane Domain: It also has a C-terminal transmembrane domain that anchors it to intracellular membranes, particularly the outer mitochondrial membrane.
• Alpha Helices: The protein is predominantly composed of alpha helices that contribute to its three-dimensional structure, facilitating the formation of heterodimers with pro-apoptotic proteins.

Classification and Subtypes

BCL2L2 is classified under the BCL-2 family, which is divided into three main subgroups:

• Anti-Apoptotic Proteins: This subgroup includes BCL2, BCL-XL, MCL1, and BCL-W (BCL2L2), all of which prevent apoptosis by binding and inhibiting pro-apoptotic proteins.
• Pro-Apoptotic Effector Proteins: Proteins such as BAX and BAK that promote apoptosis by permeabilizing the mitochondrial membrane.
• BH3-Only Proteins: A subgroup that includes BID, BIM, and PUMA, which promote apoptosis by antagonizing anti-apoptotic BCL-2 family members.

Function and Biological Significance

• Apoptosis Regulation: BCL2L2 primarily functions to inhibit apoptosis, contributing to cell survival. It achieves this by binding to and neutralizing pro-apoptotic proteins like BAX and BAK, preventing mitochondrial outer membrane permeabilization (MOMP).
• Cellular Stress Response: BCL2L2 is involved in the cellular response to various stressors, helping cells to survive under adverse conditions.
• Cancer: Overexpression of BCL2L2 has been observed in several types of cancer, including colorectal cancer and lymphoma, where it contributes to tumor growth and resistance to chemotherapy.

Clinical Issues

• Cancer Therapy Resistance: The anti-apoptotic function of BCL2L2 can lead to resistance against cancer therapies that induce apoptosis, such as chemotherapy and radiation therapy. This makes it a potential target for cancer treatment.
• Therapeutic Targeting: Inhibitors of BCL2L2 are being investigated as potential therapeutic agents to enhance the efficacy of existing cancer treatments by promoting apoptosis in cancer cells.

Summary

BCL2-like 2 (BCL2L2), also known as BCL-W, is a critical anti-apoptotic protein in the BCL-2 family. It inhibits apoptosis by interacting with and neutralizing pro-apoptotic proteins, thus promoting cell survival. BCL2L2 is structurally characterized by multiple BH domains and a transmembrane domain that anchors it to mitochondrial membranes. Its overexpression is linked to various cancers, contributing to tumor growth and therapy resistance. Understanding the function and regulation of BCL2L2 is essential for developing targeted cancer therapies aimed at overcoming resistance to apoptosis.