Protein ubiquitination extensively modulates protein functions and controls various biological processes, such as protein degradation, signal transduction, transcription, and DNA repair. Ubiquitination is a reversible post-translational modification, and deubiquitinating enzymes cleave ubiquitin from proteins. Ubiquitin-specific peptidase 46 (USP46), a deubiquitinase, is highly expressed in the brain and regulates neural functions. Deleting lysine 92 (ΔK92) in USP46 reduces murine depression-like behavior in the tail suspension test. However, the molecular basis for USP46's role in regulating neural function has not yet been fully understood. Here we employed a proximity-dependent biotinylation approach to characterize the USP46 protein interaction partners. Using homology-independent targeted integration (HITI), a genome editing technique, we established knockin cell lines that stably express USP46 wildtype- or ΔK92-biotin ligase fusion protein. We identified 286 candidate interaction partners, including well-known binding partners of USP46. Although there were no obvious differences in the interactome of USP46 between wildtype and ΔK92, a gene ontology analysis revealed that centrosome-related proteins were significantly enriched in the proximal proteins of USP46. Several centrosome-related proteins were bound to USP46 in Neuro2a cells, but their protein expression levels were not affected in the brains of USP46-deficient mice. These results uncover a potential relationship between USP46 and centrosome regulation independently of protein stabilization.
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http://dx.doi.org/10.1002/2211-5463.13918 | DOI Listing |
Discov Oncol
November 2024
Research Center of Clinical Laboratory Science, Bengbu Medical University, Bengbu, 233030, China.
FEBS Open Bio
October 2024
Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, Sanda, Japan.
Neural Regen Res
August 2025
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Medical College, Qingdao University, Qingdao, Shandong Province, China.
JOURNAL/nrgr/04.03/01300535-202508000-00031/figure1/v/2024-09-30T120553Z/r/image-tiff The protein connector enhancer of kinase suppressor of Ras 2 (CNKSR2), present in both the postsynaptic density and cytoplasm of neurons, is a scaffolding protein with several protein-binding domains. Variants of the CNKSR2 gene have been implicated in neurodevelopmental disorders, particularly intellectual disability, although the precise mechanism involved has not yet been fully understood.
View Article and Find Full Text PDFJ Genet Genomics
September 2024
Scientific Research Center, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China. Electronic address:
Laterality is a crucial physiological process intricately linked to the cilium-centrosome complex during embryo development. Defects in the process can result in severe organ mispositioning. Coiled-coil domain containing 141 (CCDC141) has been previously known as a centrosome-related gene, but its role in left-right (LR) asymmetry has not been characterized.
View Article and Find Full Text PDFPancreatology
September 2024
Department of Science and Technology, University of Sannio, Benevento, Italy; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Complutense University Madrid, 28040, Madrid, Spain. Electronic address:
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the leading cause of cancer death worldwide. PDACs are characterized by centrosome aberrations, but whether centrosome-related genes influence patient outcomes has not been tested.
Methods: Publicly available RNA-sequencing data of patients diagnosed with PDAC were interrogated with unsupervised approaches to identify centrosome protein-encoding genes with prognostic relevance.
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