chromatin-bound cullin-ring ligases: regulatory roles in dna replication and potential targeting for cancer therapy

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ID: 199465
2018
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Abstract
Cullin-RING (Really Interesting New Gene) E3 ubiquitin ligases (CRLs), the largest family of E3 ubiquitin ligases, are functional multi-subunit complexes including substrate receptors, adaptors, cullin scaffolds, and RING-box proteins. CRLs are responsible for ubiquitination of ~20% of cellular proteins and are involved in diverse biological processes including cell cycle progression, genome stability, and oncogenesis. Not surprisingly, cullins are deregulated in many diseases and instances of cancer. Recent studies have highlighted the importance of CRL-mediated ubiquitination in the regulation of DNA replication/repair, including specific roles in chromatin assembly and disassembly of the replication machinery. The development of novel therapeutics targeting the CRLs that regulate the replication machinery and chromatin in cancer is now an attractive therapeutic strategy. In this review, we summarize the structure and assembly of CRLs and outline their cellular functions and their diverse roles in cancer, emphasizing the regulatory functions of nuclear CRLs in modulating the DNA replication machinery. Finally, we discuss the current strategies for targeting CRLs against cancer in the clinic.
Reference Key
jang2018frontierschromatin-bound Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Sang-Min Jang;Christophe E. Redon;Mirit I. Aladjem
Journal biopsychosocial medicine
Year 2018
DOI
10.3389/fmolb.2018.00019
URL
http://journal.frontiersin.org/article/10.3389/fmolb.2018.00019/full
Keywords
Cancer dna replication chromatin

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