The emerging role of Cockayne group A and B proteins in ubiquitin/proteasome-directed protein degradation

• Published in: Mechanisms of ageing and development 2021-04, Vol.195, p.111466-111466, Article 111466
• Main Authors: Paccosi, Elena, Proietti-De-Santis, Luca
• Format: Article
• Language: English
• Subjects: Cell division and aging; Cockayne syndrome ubiquitination-degradation in aging CSA and CSB; DNA repair
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/j.mad.2021.111466

•CSA and CSB proteins are involved in nuclear and mitochondrial DNA metabolic pathways, such as DNA repair and transcription.•When mutated, CSA and CSB are the cause of a devastating progeroid syndrome, Cockayne syndrome.•CS mediated ubiquitin/proteasome degradation occurs in processes as DNA repair, transcription and cell division.•Our hypothesis is to reconcile the overall CS phenotypes within the role of CSA and CSB in ubiquitin/proteasome degradation. When mutated, csa and csb genes are responsible of the complex phenotype of the premature aging Cockayne Syndrome (CS). Our working hypothesis is to reconcile the multiple cellular and molecular phenotypes associated to CS within the unifying molecular function of CSA and CSB proteins in the cascade of events leading to ubiquitin/proteasome–directed protein degradation, which occurs in processes as DNA repair, transcription and cell division. This achievement may reasonably explain the plethora of cellular UPS-regulated functions that result impaired when either CSA or CSB are mutated and suggestively explains part of their pleiotropic effect. This review is aimed to solicit the interest of the scientific community in further investigating this aspect, since we believe that the identification of the ubiquitin-proteasome machinery as a new potential therapeutic target, able to comprehensively face the different molecular aspects of CS, whether confirmed and corroborated by in vivo studies, would open a promising avenue to design effective therapeutic intervention.