Bclw

BCL-W, also known as BCL2-like 2, is an anti-apoptotic member of the BCL-2 protein family. In mammals it is encoded by the BCL2L2 gene. The protein localizes primarily to the outer mitochondrial membrane, with possible presence at other intracellular membranes, and functions to promote cell survival.

Its pro-survival activity is achieved through the characteristic BCL-2 family mechanism: the protein contains BH1-4 domains and a C-terminal hydrophobic tail that anchors it to membranes. BCL-W binds to and neutralizes pro-apoptotic BCL-2 family proteins, including Bax and Bak, and sequesters BH3-only proteins such as BIM, BID, BAD, and PUMA, thereby preventing activation of mitochondrial outer membrane permeabilization.

Expression patterns of BCL-W vary by tissue and developmental stage. It is expressed in many tissues, with relatively higher levels in some hematopoietic and neural tissues. Expression can be modulated by cellular stress and signaling pathways. In cancer, overexpression of BCL-W has been observed and is associated with increased cell survival and resistance to chemotherapy and radiation; conversely, reduced levels can sensitize cells to apoptotic stimuli.

In research and clinical contexts, BCL-W is considered part of the broader BCL-2 family’s role in apoptosis regulation. Because of its anti-apoptotic function, BCL-W is a potential target for therapies aimed at promoting cell death in cancer, including the use of BH3 mimetics that antagonize anti-apoptotic BCL-2 family proteins.