Dataset Information

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

ABSTRACT: 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-XL, 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.

SUBMITTER: Hartman ML

PROVIDER: S-EPMC7174325 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hartman Mariusz L ML Czyz Malgorzata M

Cell death & disease 20200421 4

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<sub>L</sub>, and exhibits a high conformational flexibility. BCL-w level is controlled by a number of ...[more]

PMID: 32317622

Similar Datasets

Project description:Bcl-2 is an anti-apoptotic protein that promotes cell survival and resistance to cell death. Predictably, Bcl-2 as well as other anti-apoptotic Bcl-2 family members have been found to be overexpressed in a variety of human cancers. Approaches to overcome apoptotic resistance afforded by Bcl-2 in cells include anti-sense oligonucleotides, drugs that inhibit Bcl-2 function, and BH3 mimics have not been universally effective; thus, the need to understand the underlying mechanism of this resistance is vital. Glucocorticoids are stress hormones that act through their cognate receptors to control the transcription of numerous target genes, and in turn regulate a diverse array of biological processes. Synthetic glucocorticoids, such as dexamethasone, are prescribed in many chemotherapy protocols for neoplasms of lymphoid origin based on their ability to inhibit lymphocyte proliferation and promote apoptosis. However, lymphoid cells expressing Bcl-2 are resistant to glucocorticoid-induced cell death. We observed both pro- and anti-apoptotic characteristics in lymphoid cells expressing Bcl-2 following glucocorticoid treatment. These cells exhibited a profound change in their intracellular ionic composition, but a limited apoptotic ion flux and the absence of cell death. Provocatively, mimicking the loss of intracellular potassium using a low dose of a microbial toxin that acts as a potassium ionophore in combination with dexamethasone overcame the resistance afforded by Bcl-2 and killed the cells. Extending our study using other potassium ionophores revealed that direct depolarization of the mitochondria membrane potential coupled with prior treatment with glucocorticoids is the key mechanism for activating the cell death program and bypassing the resistance afforded by Bcl-2 in lymphoid cells. Finally, we show that the duration of dexamethasone pre-treatment is critical for regulating distinct genes and signaling pathways that sensitize the cells to die.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets