Targeting E3 Ubiquitin Ligases and Deubiquitinases in Ciliopathy and Cancer

Cilia are antenna-like structures present in many vertebrate cells. These organelles detect extracellular cues, transduce signals into the cell, and play an essential role in ensuring correct cell proliferation, migration, and differentiation in a spatiotemporal manner. Not surprisingly, dysregulati...

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Bibliographic Details
Published in:International journal of molecular sciences 2020-08, Vol.21 (17), p.5962
Main Authors: Shiromizu, Takashi, Yuge, Mizuki, Kasahara, Kousuke, Yamakawa, Daishi, Matsui, Takaaki, Bessho, Yasumasa, Inagaki, Masaki, Nishimura, Yuhei
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Cancer
Cell cycle
Cell differentiation
Cell proliferation
Cilia
Ciliopathies - drug therapy
Ciliopathies - metabolism
Congenital diseases
Cytoplasm
Deubiquitinating Enzymes - metabolism
Enzyme Inhibitors - pharmacology
Enzyme Inhibitors - therapeutic use
Enzymes
Genes
Humans
Intellectual disabilities
Kidney diseases
Kinases
Mutation
Neoplasms - drug therapy
Neoplasms - metabolism
Obesity
Organelles
Photoreceptors
Proteasomes
Proteins
Review
Roles
Structure-function relationships
Ubiquitin
Ubiquitin-Protein Ligases - metabolism
Ubiquitination - drug effects
Vertebrates
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Summary:Cilia are antenna-like structures present in many vertebrate cells. These organelles detect extracellular cues, transduce signals into the cell, and play an essential role in ensuring correct cell proliferation, migration, and differentiation in a spatiotemporal manner. Not surprisingly, dysregulation of cilia can cause various diseases, including cancer and ciliopathies, which are complex disorders caused by mutations in genes regulating ciliary function. The structure and function of cilia are dynamically regulated through various mechanisms, among which E3 ubiquitin ligases and deubiquitinases play crucial roles. These enzymes regulate the degradation and stabilization of ciliary proteins through the ubiquitin-proteasome system. In this review, we briefly highlight the role of cilia in ciliopathy and cancer; describe the roles of E3 ubiquitin ligases and deubiquitinases in ciliogenesis, ciliopathy, and cancer; and highlight some of the E3 ubiquitin ligases and deubiquitinases that are potential therapeutic targets for these disorders.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms21175962