Ubiquilins (Ubqlns)-a family of ubiquitin-binding proteins-are involved in several protein degradation pathways and have been implicated in various neurodegenerative diseases. Ubqln1 regulates autophagosome maturation during autophagy-mediated degradation. We now show that Ubqln4 mediates the interaction between Ubqln1 and the autophagy machinery by recruiting Ubqln1 to LC3. This targeting of Ubqln1 to autophagosomes requires the Ubqln4 UBL domain and the Ubqln1 UBA domain. This study identifies a new role for Ubqln4, expanding the role for Ubqlns in protein degradation.
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http://dx.doi.org/10.1038/embor.2013.22 | DOI Listing |
Sci Adv
January 2025
Department of Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.
View Article and Find Full Text PDFJ Virol
January 2025
College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, China.
Unlabelled: Avian leukosis virus subgroup J (ALV-J) poses a significant threat to the poultry industry; yet, our understanding of its replication and pathogenic mechanisms is limited. The Ten-Eleven Translocation 2 (TET2) is an indispensable regulatory factor in active DNA demethylation and immune response regulation. This study reports a significant and time-dependent decrease in TET2 levels following ALV-J infection and shows that the reduction of TET2 protein is mediated by the autophagy pathway.
View Article and Find Full Text PDFTrends Biochem Sci
January 2025
Department of Biomedicine, University of Bergen, Bergen, Norway; Department of Surgery, Haukeland University Hospital, Bergen, Norway. Electronic address:
The majority of eukaryotic proteins undergo N-terminal (Nt) modifications facilitated by various enzymes. These enzymes, which target the initial amino acid of a polypeptide in a sequence-dependent manner, encompass peptidases, transferases, cysteine oxygenases, and ligases. Nt modifications - such as acetylation, fatty acylations, methylation, arginylation, and oxidation - enhance proteome complexity and regulate protein targeting, stability, and complex formation.
View Article and Find Full Text PDFFood Chem Toxicol
January 2025
Department of Biochemistry, Faculty of Pharmacy, Mansoura University, 35516, Mansoura, Egypt.
Vancomycin, a glycopeptide antibiotic, is used in cases of drug-resistant bacterial infections, but unfortunately is associated with acute kidney injury (AKI). We here explore the protective potential of aprepitant against vancomycin-induced AKI. Vancomycin (500 mg/kg/i.
View Article and Find Full Text PDFJ Mol Biol
January 2025
Instituto de Investigaciones Biomédicas Sols-Morreale CSIC-UAM, 28029 Madrid, Spain. Electronic address:
A key step in autophagy is the conjugation by the E3-like Atg12-Atg5-Atg16 complex of the ubiquitin-like protein Atg8 to phosphatidylethanolamine on the autophagosomal membrane, a process known as lipidation. Previous work in yeast showed that recruitment of the E3-like complex to the preautophagosomal structure is mediated by the interaction of Atg16 with the phosphatidylinositol 3-phosphate-binding protein Atg21, and by the association of Atg12 with the scaffold protein of the Atg1 kinase complex, Atg17. Here, we conducted a reverse two-hybrid screen to identify residues in Atg17 and Atg12 critical for Atg17-Atg12 binding, and used these data to generate a docking model of Atg12-Atg5-Atg16 with the Atg17 complex.
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