Cullin 1 (CUL1) Promotes Primary Ciliogenesis through the Induction of Ubiquitin-Proteasome-Dependent Dvl2 Degradation.
Primary cilia are nonmotile cellular signal-sensing antenna-like structures composed of microtubule-based structures that distinguish them from motile cilia in structure and function. Primary ciliogenesis is regulated by various cellular signals, such as Wnt, hedgehog (Hh), and platelet-derived growth factor (PDGF). The abnormal regulation of ciliogenesis is closely related to developing ... various human diseases, including ciliopathies and cancer. This study identified a novel primary ciliogenesis factor Cullin 1 (CUL1), a core component of Skp1-Cullin-F-box (SCF) E3 ubiquitin ligase complex, which regulates the proteolysis of dishevelled 2 (Dvl2) through the ubiquitin-proteasome system. Through immunoprecipitation-tandem mass spectrometry analysis, 176 Dvl2 interacting candidates were identified, of which CUL1 is a novel Dvl2 modulator that induces Dvl2 ubiquitination-dependent degradation. Neddylation-dependent CUL1 activity at the centrosomes was essential for centrosomal Dvl2 degradation and primary ciliogenesis. Therefore, this study provides a new mechanism of Dvl2 degradation by CUL1, which ultimately leads to primary ciliogenesis, and suggest a novel target for primary cilia-related human diseases.
Mesh Terms:
Cells, Cultured, Cilia, Cullin Proteins, Dishevelled Proteins, Humans, Proteasome Endopeptidase Complex, Protein Binding, Proteolysis, SKP Cullin F-Box Protein Ligases, Signal Transduction, Ubiquitin, Ubiquitination
Cells, Cultured, Cilia, Cullin Proteins, Dishevelled Proteins, Humans, Proteasome Endopeptidase Complex, Protein Binding, Proteolysis, SKP Cullin F-Box Protein Ligases, Signal Transduction, Ubiquitin, Ubiquitination
Int J Mol Sci
Date: Jul. 15, 2021
PubMed ID: 34299191
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