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Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome

K11/K48 branched ubiquitin chains regulate protein degradation and cell cycle progression. Here, the authors report the structural basis of how such a branched ubiquitin chain is recognized by the human 26S proteasome, revealing a multivalent binding mode that underlies selective recognition.

Piotr Draczkowski
Szu-Ni Chen
Shang-Te Danny Hsu
ResearchOpen Access15 Oct 2025
Nature Communications

Volume: 16, P: 1-16
TRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation

cGAS/STING activation is linked to the induction of anti-tumor immune responses. Here the authors report a role for the deubiquitinating enzyme TRABID in regulating mitotic cell division and suppressing anti-tumor immunity, suggesting that TRABID inhibition induces micronuclei and activates cGAS/STING pathway.

Yu-Hsuan Chen
Han-Hsiun Chen
Ruey-Hwa Chen
ResearchOpen Access26 May 2023
Nature Communications

Volume: 14, P: 1-20
VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism

Autophagy and the ubiquitin–proteasome system (UPS) are cellular quality control processes, but their coordination remains unclear. Here, the authors show that branched ubiquitination of VPS34 functions as a switch between UPS and autophagy and has an important role in lipid metabolism in the liver.

Yu-Hsuan Chen
Tzu-Yu Huang
Ruey-Hwa Chen
ResearchOpen Access26 Feb 2021
Nature Communications

Volume: 12, P: 1-19
Identification of disease-linked hyperactivating mutations in UBE3A through large-scale functional variant analysis

UBE3A gene dysregulation is associated with neurodevelopmental disorders, but predicting the function of UBE3A variants remains difficult. The authors use a high-throughput assay to categorize variants by functional activity, and show that UBE3A hyperactivity increases the risk of neurodevelopmental disease.

Kellan P. Weston
Xiaoyi Gao
Jason J. Yi
ResearchOpen Access23 Nov 2021
Nature Communications

Volume: 12, P: 1-15
Deubiquitinase activity is required for the proteasomal degradation of misfolded cytosolic proteins upon heat-stress

Ubiquitination of misfolded proteins usually results in protein degradation. Here, the authors show that two deubiquitinases—enzymes that remove ubiquitin—are required for the proteasomal degradation of misfolded proteins in response to heat-shock in yeast.

Nancy N. Fang
Mang Zhu
Thibault Mayor
ResearchOpen Access04 Oct 2016
Nature Communications

Volume: 7, P: 1-16
Correction: PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target

Shaifali Singh
Nai Yang Yeat
Ruey-Hwa Chen
Amendments and CorrectionsOpen Access02 Jul 2024
Cell Death & Disease

Volume: 15, P: 1
A cascading activity-based probe sequentially targets E1–E2–E3 ubiquitin enzymes

A ubiquitin analog used as an activity-based probe of ubiquitin conjugation enzymes, E1, E2 and E3 covalently traps these enzymes without transfer to substrates. The probes can be used in structural and functional studies and to visualize enzyme activity in cells.

Monique P C Mulder
Katharina Witting
Huib Ovaa
Research16 May 2016
Nature Chemical Biology

Volume: 12, P: 523-530
Filamentous chemokine CCL5 structure and the functional aspects

Yi-Ting Yuan
Tzu-Ching Guo
Shih-Che Sue
ResearchOpen Access19 Apr 2025
Scientific Reports

Volume: 15, P: 1-13
PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target

Shaifali Singh
Nai Yang Yeat
Ruey-Hwa Chen
ResearchOpen Access11 Oct 2023
Cell Death & Disease

Volume: 14, P: 1-17
Unveiling transient protein-protein interactions that modulate inhibition of alpha-synuclein aggregation by beta-synuclein, a pre-synaptic protein that co-localizes with alpha-synuclein

Maria K. Janowska
Kuen-Phon Wu
Jean Baum
ResearchOpen Access19 Oct 2015
Scientific Reports

Volume: 5, P: 1-10

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Structural basis of K11/K48-branched ubiquitin chain recognition by the human 26S proteasome

TRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation

VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID regulates autophagy, proteostasis and liver metabolism

Identification of disease-linked hyperactivating mutations in UBE3A through large-scale functional variant analysis

Deubiquitinase activity is required for the proteasomal degradation of misfolded cytosolic proteins upon heat-stress

Correction: PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target

A cascading activity-based probe sequentially targets E1–E2–E3 ubiquitin enzymes

Filamentous chemokine CCL5 structure and the functional aspects

PTPN23 ubiquitination by WDR4 suppresses EGFR and c-MET degradation to define a lung cancer therapeutic target

Unveiling transient protein-protein interactions that modulate inhibition of alpha-synuclein aggregation by beta-synuclein, a pre-synaptic protein that co-localizes with alpha-synuclein

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