An efficient method for the assembly of polyUb chains using auxiliary-modified Ub isomers is reported. This strategy takes advantages of auxiliary-mediated native chemical ligation between the distal Ub C-terminal hydrazide and the auxiliary of proximal Ub. Using removable protecting groups, Lys48-linked and Lys6-linked tri-Ub and even a mixed-linkage Lys6, Lys48-linked triUb in multimilligram quantities was made. These results demonstrate that this strategy yields natural polyubiquitin chains of desired length and linkage by using Ub isomer.
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http://dx.doi.org/10.1021/acs.orglett.7b03515 | DOI Listing |
J Integr Plant Biol
January 2025
National Key Laboratory for Rice Biology and Breeding, Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.
The rice E3 ubiquitin ligases OsCIE1 and IPI7 mediate the non-proteolytic polyubiquitination of the pattern-recognition receptor kinase OsCERK1 and the transcription factor IPA1, respectively, in response to Magnaporthe oryzae infection, thereby fine-tuning rice growth-immunity trade-offs.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, Collaborative Innovation Center of Cell Biology in Universities of Shandong, Department of Biochemistry and Molecular Biology, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China.
Poly(ADP-ribose) polymerase 1 (PARP1) plays a crucial role in DNA repair and genomic stability maintenance. However, the regulatory mechanisms governing PARP1 activity, particularly through deubiquitination, remain poorly elucidated. Using a deubiquitinase (DUB) library binding screen, we identified cylindromatosis (CYLD) as a bona fide DUB for PARP1 in breast cancer cells.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, P. R. China.
Defective clearance and accumulation of α-synuclein (α-Syn) is the key pathogenic factor in Parkinson's disease (PD). Recent studies emphasize the importance of E3 ligases in regulating the degradation of α-Syn. However, the molecular mechanisms by which deubiquitinases regulate α-Syn degradation are scarcely studied.
View Article and Find Full Text PDFMol Biol Cell
December 2024
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA.
Autophagy is an essential cellular recycling process that maintains protein and organelle homeostasis. ATG9A vesicle recruitment is a critical early step in autophagy to initiate autophagosome biogenesis. The mechanisms of ATG9A vesicle recruitment are best understood in the context of starvation-induced non-selective autophagy, whereas less is known about the signals driving ATG9A vesicle recruitment to autophagy initiation sites in the absence of nutrient stress.
View Article and Find Full Text PDFEur J Immunol
December 2024
Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Tumor cell-intrinsic ubiquitin-conjugating enzyme Ubc13 promotes tumorigenesis, yet how Ubc13 in immune cell compartments regulates tumor progression remains elusive. Here, we show that myeloid-specific deletion of Ubc13 (Ubc13Lyz2) leads to accelerated transplanted lung tumor growth in mice. Compared with their littermate controls, tumor-bearing Ubc13Lyz2 mice had lower proliferation and effector function of CD8 T lymphocytes, accompanied by increased infiltration of myeloid-derived suppressor cells within the tumor microenvironment.
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