Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
Abstract: Post‐translational modifications of Tau are emerging as key players in determining the onset and progression of different tauopathies such as Alzheimer's disease, and are recognized to mediate the structural diversity of the disease‐specific Tau amyloids. Here we show that the E3 ligase CHIP catalyzes the site‐specific ubiquitination of Tau filaments both in vitro and in cellular models, proving that also Tau amyloid aggregates are direct substrate of PTMs. Transmission electron microscopy and mass spectrometry analysis on ubiquitin‐modified Tau amyloids revealed that the conformation of the filaments restricts CHIP‐mediated ubiquitination to specific positions of the repeat domain, while only minor alterations in the structure of the fibril core were inferred using seeding experiments in vitro and in a cell‐based tauopathy model. Overexpression of CHIP significantly increased the ubiquitination of exogenous PHF, proving that the ligase can interact and modify Tau aggregates also in a complex cellular environment.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP ; day:10 ; month:11 ; year:2023 ; extent:13
Angewandte Chemie / International edition. International edition ; (10.11.2023) (gesamt 13)
- Creator
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Parolini, Francesca
Ataie Kachoie, Elham
Leo, Giulia
Civiero, Laura
Bubacco, Luigi
Arrigoni, Giorgio
Munari, Francesca
Assfalg, Michael
D'Onofrio, Mariapina
Capaldi, Stefano
- DOI
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10.1002/anie.202310230
- URN
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urn:nbn:de:101:1-2023111114034483832332
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:52 AM CEST
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Associated
- Parolini, Francesca
- Ataie Kachoie, Elham
- Leo, Giulia
- Civiero, Laura
- Bubacco, Luigi
- Arrigoni, Giorgio
- Munari, Francesca
- Assfalg, Michael
- D'Onofrio, Mariapina
- Capaldi, Stefano
Other Objects (12)
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
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Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1
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Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
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The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma
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An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α
PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu
E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2
Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1
Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12
SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma
NAP1L1 regulates BIRC2 ubiquitination modification via E3 ubiquitin ligase UBR4 and hence determines hepatocellular carcinoma progression
An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α
PHB2 promotes SHIP2 ubiquitination via the E3 ligase NEDD4 to regulate AKT signaling in gastric cancer
Site‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
The E3 ubiquitin ligase MID1 catalyzes ubiquitination and cleavage of Fu
E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2
Structure-guided engineering enables E3 ligase-free and versatile protein ubiquitination via UBE2E1
Control of TGFβ signalling by ubiquitination independent function of E3 ubiquitin ligase TRIP12
SCFβ-TRCP E3 ubiquitin ligase targets the tumor suppressor ZNRF3 for ubiquitination and degradation
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
Structural Basis for Chaperone‐Independent Ubiquitination of Tau Protein by Its E3 Ligase CHIP
The E3 ligase TRIM26 suppresses ferroptosis through catalyzing K63-linked ubiquitination of GPX4 in glioma
NAP1L1 regulates BIRC2 ubiquitination modification via E3 ubiquitin ligase UBR4 and hence determines hepatocellular carcinoma progression
An E3 ligase TRIM1 promotes colorectal cancer progression via K63-linked ubiquitination and activation of HIF1α