Illumination of understudied ciliary kinases.
| Title: | Illumination of understudied ciliary kinases. |
|---|---|
| Authors: | Flax RG; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; Rosston P; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; Rocha C; The Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC, Canada.; Anderson B; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; Capener JL; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; Durcan TM; The Neuro's Early Drug Discovery Unit (EDDU), McGill University, Montreal, QC, Canada.; Drewry DH; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; UNC Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; Prinos P; Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada.; Axtman AD; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. |
| Source: | Frontiers in molecular biosciences [Front Mol Biosci] 2024 Mar 08; Vol. 11, pp. 1352781. Date of Electronic Publication: 2024 Mar 08 (Print Publication: 2024). |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101653173 Publication Model: eCollection Cited Medium: Print ISSN: 2296-889X (Print) Linking ISSN: 2296889X NLM ISO Abbreviation: Front Mol Biosci Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Lausanne : Frontiers Media S.A., [2014]- |
| Abstract: | Cilia are cellular signaling hubs. Given that human kinases are central regulators of signaling, it is not surprising that kinases are key players in cilia biology. In fact, many kinases modulate ciliogenesis, which is the generation of cilia, and distinct ciliary pathways. Several of these kinases are understudied with few publications dedicated to the interrogation of their function. Recent efforts to develop chemical probes for members of the cyclin-dependent kinase like (CDKL), never in mitosis gene A (NIMA) related kinase (NEK), and tau tubulin kinase (TTBK) families either have delivered or are working toward delivery of high-quality chemical tools to characterize the roles that specific kinases play in ciliary processes. A better understanding of ciliary kinases may shed light on whether modulation of these targets will slow or halt disease onset or progression. For example, both understudied human kinases and some that are more well-studied play important ciliary roles in neurons and have been implicated in neurodevelopmental, neurodegenerative, and other neurological diseases. Similarly, subsets of human ciliary kinases are associated with cancer and oncological pathways. Finally, a group of genetic disorders characterized by defects in cilia called ciliopathies have associated gene mutations that impact kinase activity and function. This review highlights both progress related to the understanding of ciliary kinases as well as in chemical inhibitor development for a subset of these kinases. We emphasize known roles of ciliary kinases in diseases of the brain and malignancies and focus on a subset of poorly characterized kinases that regulate ciliary biology.; (Copyright © 2024 Flax, Rosston, Rocha, Anderson, Capener, Durcan, Drewry, Prinos and Axtman.) |
| Competing Interests: | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Grant Information: | R01 CA273095 United States CA NCI NIH HHS; R03 TR003386 United States TR NCATS NIH HHS |
| Contributed Indexing: | Keywords: cancer; chemical probe; cilia; ciliogenesis; ciliopathy; kinase; neurological disorder; understudied |
| Entry Date(s): | Date Created: 20240325 Latest Revision: 20240712 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10958382 |
| DOI: | 10.3389/fmolb.2024.1352781 |
| PMID: | 38523660 |
| Database: | MEDLINE |
Journal Article; Review