Ubiquitin-proteasome pathway mediated regulation of Bcl-2 family: effects and therapeutic approaches

Abstract

Proteasomal degradation of proteins represents an important regulatory mechanism in maintaining healthy homeostasis in cells. Deregulation of the ubiquitin-proteasome system is associated with various diseases as it controls protein abundance and turnover in cells. Furthermore, proteasomal regulation of protein turnover rate can determine the cell’s response to external stimuli. To this end, the Bcl-2 family of proteins is an important group of proteins involved in mediating cell survival or cell death in response to external stimuli. Aberrant overexpression of anti-apoptotic proteins or deletion of pro-apoptotic proteins can lead to the development of cancer. Unsurprisingly, proteasomal degradation of Bcl-2 proteins also serves as an important factor to regulating the level of Bcl-2 proteins and thereby affecting the functional outcome of cell death. Thus, this review aims to highlight the regulation of Bcl-2 family of proteins with particular emphasis on the proteasomal-mediated degradation pathways and the current literature on the therapeutic approaches targeting the proteasome system.