What is the Difference Between Bcl-2 and Bcl-xL

The key difference between Bcl-2 and Bcl-xL is that the expression of Bcl-2 happens only in differentiated human mesenchymal stem cells, while the expression of Bcl-xL happens in both undifferentiated and differentiated human mesenchymal stem cells.

Apoptosis is a method of eliminating unwanted or abnormal cells from the body of multicellular organisms. It is kind of a programmed cell death that is a carefully controlled process. A series of biochemical events take place during apoptosis. In cancer cells, apoptosis is blocked. In other words, dysregulated apoptosis or avoidance of apoptosis is a critical reason for tumourigenesis.

Inappropriate apoptosis may be a reason for many human diseases, including neurodegenerative diseases, ischemic damage, autoimmune disorders, and many types of cancer. B-cell lymphoma-2 (Bcl-2) protein family is an antiapoptotic protein family in which Bcl-2 and Bcl-xL are two members. They are located at endoplasmic reticulum. They prevent mitochondrial outer membrane permeabilization in order to promote cell survival. Therefore, they participate in inhibiting mitochondrial-dependent extrinsic and intrinsic cell death pathways. While regulating apoptosis, they promote cell survival.

CONTENTS

1. Overview and Key Difference
2. What is Bcl-2
3. What is Bcl-xL
4. Similarities – Bcl-2 and Bcl-xL
5. Bcl-2 vs Bcl-xL in Tabular Form
6. Summary – Bcl-2 vs Bcl-xL

What is Bcl-2?

Bcl-2 is the prototypic antiapoptotic protein that is a member of the Bcl-2 family. It is also known as a B-cell lymphoma 2 protein. There are two isoforms of Bcl-2 protein. Bcl-2 blocks apoptosis and promotes the survival of cells. The gene BCL2 codes for Bcl-2 protein, and this gene is located on chromosome 18.

Translocation of the gene BCL2 from chromosome 18 to chromosome 14 is associated with many B-cell leukemias and lymphomas. Overexpression of Bcl-2 protein or deregulated expression of Bcl-2 is responsible for keeping cancer cells from dying. This is because overexpression of Bcl-2 inhibits apoptotic cell death. However, loss of Bcl-2 proteins has a significant effect on certain normal tissue homeostasis and development. For example, the survival of renal epithelial stem cells during embryogenesis, melanocyte progenitors, and mature B and T lymphocytes depend on Bcl-2. Naive T cells rely on Bcl-2 for survival.

What is Bcl-xL?

B-cell lymphoma-extra large or Bcl-xL is a member protein of Bcl-2 antiapoptotic protein family. This protein is coded by the BCL2-like 1 gene. Bcl-xL is found in the outer mitochondrial membrane. Similar to Bcl-2 protein, Bcl-xL also promotes cell survival by inhibiting apoptosis.

Bcl-xL inhibits apoptosis by preventing the release of mitochondrial contents, especially cytochrome c. It is done by controlling the mitochondrial membrane permeability. Bcl-xL over-expression can be seen in cancer cells. Bcl-xL is the functional antiapoptotic protein in hepatocytes. During hepatocyte regeneration, Bcl-xL expression is seen while Bcl-2 is not detected.

What are the Similarities Between Bcl-2 and Bcl-xL?

• Bcl-2 and Bcl-xL are anti-apoptotic proteins.
• They are members of the anti-apoptotic BcL-2 protein family.
• They share a similarity in four BCL-2 homology (BH) domains and similar 3D structures.
• They play important roles in cell death.
• In fact, they work together to regulate apoptosis, cell cycle arrest, and cell cycle entry.
• They also play important roles in cancer development.
• Both types of proteins can arrest cells at the G0 phase and delay the entry into the S phase.
• They delay the S phase by lengthening either G0 or G1 phase.

What is the Difference Between Bcl-2 and Bcl-xL?

Bcl-2 is an antiapoptotic protein coded by the gene BCL2 while Bcl-xL is a mitochondrial transmembrane protein that is an antiapoptotic protein coded by BCL2-like 1 gene. Moreover, Bcl-xL is about ten times more functional than Bcl-2 when induced by Doxorubicin. The key difference between Bcl-2 and Bcl-xL is that Bcl-2 expression can be seen only in differentiated hMSCs, while Bcl-xL expression can be seen in both undifferentiated and differentiated hMSCs.

The below infographic presents the differences between Bcl-2 and Bcl-xL in tabular form for side by side comparison.

Summary – Bcl-2 vs Bcl-xL

The evasion of apoptosis is critical for the sustained growth of cancers. Bcl-2 and Bcl-xL are two anti-apoptotic molecules that have anti-proliferative effects. They play important roles in inhibiting apoptosis and cell proliferation. The key difference between Bcl-2 and Bcl-xL is that the expression of Bcl-2 happens only in differentiated human mesenchymal stem cells, while the expression of Bcl-xL happens in both undifferentiated and differentiated human mesenchymal stem cells.

Reference:

1. Kelly, P N, and A Strasser. “The Role of Bcl-2 and Its pro-Survival Relatives in Tumourigenesis and Cancer Therapy.” Cell Death and Differentiation, Nature Publishing Group, Sept. 2011.
2. “Bcl-2.” Wikipedia, Wikimedia Foundation, 21 Aug. 2021.

Image Courtesy:

1. “BCL-2 human” By Dan Cojocari – own, PyMol, Illustrator (CC BY-SA 3.0) via Commons Wikimedia
2. “Bcl-xl” By R. M. – Own work (Public Domain) via Commons Wikimedia