Ubiquitin proteasome system (UPS): a crucial determinant of the epigenetic landscape in cancer

The ubiquitin proteasome system (UPS), comprising of ubiquitinases, deubiquitinases and 26S proteasome plays a significant role in directly or indirectly regulating epigenetic players. DNA-templated processes like replication, repair and transcription require chromatin decondensation to allow access to specific DNA sequence. A thorough survey of literary articles in PubMed database revealed that the UPS functions as a key regulator, determining the precise state of open and closed chromatin by influencing histones and histone modifiers through proteolytic or non-proteolytic means. However, a comprehensive understanding of how specific UPS components affect particular epigenetic pathways in response to environmental cues remains underexplored. This axis holds substantial potential for deciphering mechanisms of tumorigenesis. Although our current knowledge is limited, it can still guide the development of novel therapeutic strategies that can potentially bridge the gap between cancer chemotherapeutics in bench and bedside.