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- Title
Modulation of Primary Cilia by Alvocidib Inhibition of CILK1.
- Authors
Wang, Elena X.; Turner, Jacob S.; Brautigan, David L.; Fu, Zheng
- Abstract
The primary cilium provides cell sensory and signaling functions. Cilia structure and function are regulated by ciliogenesis-associated kinase 1 (CILK1). Ciliopathies caused by CILK1 mutations show longer cilia and abnormal Hedgehog signaling. Our study aimed to identify small molecular inhibitors of CILK1 that would enable pharmacological modulation of primary cilia. A previous screen of a chemical library for interactions with protein kinases revealed that Alvocidib has a picomolar binding affinity for CILK1. In this study, we show that Alvocidib potently inhibits CILK1 (IC50 = 20 nM), exhibits selectivity for inhibition of CILK1 over cyclin-dependent kinases 2/4/6 at low nanomolar concentrations, and induces CILK1-dependent cilia elongation. Our results support the use of Alvocidib to potently and selectively inhibit CILK1 to modulate primary cilia.
- Subjects
CILIA &; ciliary motion; HEDGEHOG signaling proteins; PROTEIN kinases; CHEMICAL libraries; PROTEIN-protein interactions
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 15, p8121
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23158121