BCL2 Human

B-Cell Leukemia/Lymphoma 2 (BCL-2) is a protein that plays a crucial role in regulating apoptosis, the process of programmed cell death. This protein is encoded by the BCL2 gene located on human chromosome 18q21 . BCL-2 is an anti-apoptotic molecule, meaning it helps cells avoid apoptosis, which is a key feature in the development and progression of various cancers .

The BCL-2 gene was first identified as the anonymous partner of the immunoglobulin heavy chain locus in the typical translocation seen in follicular lymphoma: t(14;18) . Initially, the function of BCL-2 was unknown, but it was later discovered that the BCL-2 protein protects cells from apoptosis when overexpressed . This discovery was significant as it was the first mammalian gene product associated with apoptosis, leading to extensive research into the mechanisms of cell death and cancer .

BCL-2 functions by inhibiting the initiation of apoptosis. It achieves this by binding to and holding in check the key cell death effector proteins, BAX and BAK . When activated, BAX and BAK congregate on the outer membrane of the mitochondria, creating pores that permeabilize and depolarize the organelle. This process releases cytochrome C and activates caspases, which execute the destruction of cells in a manner recognized as apoptosis .

BCL-2 is variably highly expressed in many hematological malignancies, providing protection from cell death induced by oncogenic and external stresses . The overexpression of BCL-2 is a hallmark of several cancers, including chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) . The protein’s ability to inhibit apoptosis allows cancer cells to survive longer than they should, contributing to tumor growth and resistance to conventional therapies .

Given its central role in preventing apoptosis, BCL-2 has become a significant target for cancer therapy. Venetoclax is the first selective BCL-2 inhibitor and the first of a new class of anticancer drugs known as BH3-mimetics . Venetoclax has been approved for routine clinical practice in the treatment of CLL and AML . By inhibiting BCL-2, venetoclax triggers apoptosis in cancer cells, offering a promising therapeutic strategy .

Human recombinant BCL-2 is a form of the protein that is produced through recombinant DNA technology. This involves inserting the BCL2 gene into a suitable expression system, such as Escherichia coli (E. coli), to produce the protein in large quantities . Recombinant BCL-2 is used in research to study its function, interactions, and potential as a therapeutic target.