Alterations of the interactome of Bcl-2 proteins in breast cancer at the transcriptional, mutational and structural level

by Simon Mathis K ønig, Vendela Rissler, Thilde Terkelsen, Matteo Lambrughi, Elena Papaleo Apoptosis is an essential defensive mechanism against tumorigenesis. Proteins of the B-cell lymphoma-2 (Bcl-2) family regulate programmed cell death by the mitochondrial apoptosis pathway. In response to intracellular stress, the apoptotic balance is governed by interactions of three distinct subg roups of proteins; the activator/sensitizer BH3 (Bcl-2 homology 3)-only proteins, the pro-survival, and the pro-apoptotic executioner proteins. Changes in expression levels, stability, and functional impairment of pro-survival proteins can lead to an imbalance in tissue homeostasis. Their overexpres sion or hyperactivation can result in oncogenic effects. Pro-survival Bcl-2 family members carry out their function by binding the BH3 short linear motif of pro-apoptotic proteins in a modular way, creating a complex network of protein-protein interactions. Their dysfunction enables cancer cells to evade cell death. The critical role of Bcl-2 proteins in homeostasis and tumorigenesis, coupled with mounting insight in their structural properties, make them therapeutic targets of interest. A better understanding of gene expression, mutational profile, and molecular mechanisms of pro-survival Bcl -2 proteins in different cancer types, could help to clarify their role in cancer development and may guide advancement in drug discovery. Here, we shed light on the pro-survival Bcl-2 proteins in breast ca...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research