BCL-w: apoptotic and non-apoptotic role in health and disease

The Bcl-2 Family of proteins integrates signals that trigger either cell survival or Apoptosis. The balance between pro-survival and pro-apoptotic proteins is important for tissue development and homeostasis, while impaired Apoptosis contributes to several pathologies and can be a barrier against effective treatment. Bcl-W is an anti-apoptotic protein that shares a sequence similarity with BCL-X_L, and exhibits a high conformational flexibility. Bcl-W level is controlled by a number of signaling pathways, and the repertoire of transcriptional regulators largely depends on the cellular and developmental context. As only a few disease-relevant genetic alterations of BCL2L2 have been identified, increased levels of Bcl-W might be a consequence of abnormal activation of signaling cascades involved in the regulation of Bcl-W expression. In addition, Bcl-W transcript is a target of a plethora of miRNAs. Besides its originally recognized pro-survival function during spermatogenesis, Bcl-W has been envisaged in different types of normal and diseased cells as an anti-apoptotic protein. Bcl-W contributes to survival of senescent and drug-resistant cells. Its non-apoptotic role in the promotion of cell migration and invasion has also been elucidated. Growing evidence indicates that a high Bcl-W level can be therapeutically relevant in neurodegenerative disorders, neuron dysfunctions and after small intestinal resection, whereas Bcl-W inhibition can be beneficial for Cancer patients. Although several drugs and natural compounds can bi-directionally affect Bcl-W level, agents that selectively target Bcl-W are not yet available. This review discusses current knowledge on the role of Bcl-W in health, non-cancerous diseases and Cancer.