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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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| Published in: | International journal of molecular sciences 2020-08, Vol.21 (17), p.5962 |
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| container_issue | 17 |
| container_start_page | 5962 |
| container_title | International journal of molecular sciences |
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| creator | Shiromizu, Takashi Yuge, Mizuki Kasahara, Kousuke Yamakawa, Daishi Matsui, Takaaki Bessho, Yasumasa Inagaki, Masaki Nishimura, Yuhei |
| description | 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. |
| doi_str_mv | 10.3390/ijms21175962 |
| format | article |
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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21175962</identifier><identifier>PMID: 32825105</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>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</subject><ispartof>International journal of molecular sciences, 2020-08, Vol.21 (17), p.5962</ispartof><rights>2020. 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| 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 |
| title | Targeting E3 Ubiquitin Ligases and Deubiquitinases in Ciliopathy and Cancer |
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