The Ubiquitin Proteasome System in Genome Stability and Cancer
Open Access
- 6 May 2021
- Vol. 13 (9), 2235
- https://doi.org/10.3390/cancers13092235
Abstract
Faithful DNA replication during cellular division is essential to maintain genome stability and cells have developed a sophisticated network of regulatory systems to ensure its integrity. Disruption of these control mechanisms can lead to loss of genomic stability, a key hallmark of cancer. Ubiquitination is one of the most abundant regulatory post-translational modifications and plays a pivotal role in controlling replication progression, repair of DNA and genome stability. Dysregulation of the ubiquitin proteasome system (UPS) can contribute to the initiation and progression of neoplastic transformation. In this review we provide an overview of the UPS and summarize its involvement in replication and replicative stress, along with DNA damage repair. Finally, we discuss how the UPS presents as an emerging source for novel therapeutic interventions aimed at targeting genomic instability, which could be utilized in the treatment and management of cancer.Keywords
Funding Information
- Leukaemia and Lymphoma NI (R2418CNR)
This publication has 125 references indexed in Scilit:
- Polyubiquitinated PCNA Recruits the ZRANB3 Translocase to Maintain Genomic Integrity after Replication StressMolecular Cell, 2012
- Hallmarks of Cancer: The Next GenerationCell, 2011
- The Structure‐Based Design of Mdm2/Mdmx–p53 Inhibitors Gets SeriousAngewandte Chemie, 2011
- DNA Damage ResponseCold Spring Harbor Perspectives in Biology, 2010
- Rnf8 deficiency impairs class switch recombination, spermatogenesis, and genomic integrity and predisposes for cancerThe Journal of Experimental Medicine, 2010
- The DNA-damage response in human biology and diseaseNature, 2009
- Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forksProceedings of the National Academy of Sciences of the United States of America, 2008
- Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancerNature Reviews Cancer, 2008
- Cdc6 Stability Is Regulated by the Huwe1 Ubiquitin Ligase after DNA DamageMolecular Biology of the Cell, 2007
- Ubiquitin and SUMO systems in the regulation of mitotic checkpointsTrends in Biochemical Sciences, 2006