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p(HGNC:OTUB1)

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Entity

Name
OTUB1
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 1

Tau interactome mapping based identification of Otub1 as Tau deubiquitinase involved in accumulation of pathological Tau forms in vitro and in vivo v1.0.0

In-Edges 2

a(HBP:"Tau aggregates") negativeCorrelation p(HGNC:OTUB1) View Subject | View Object

Interestingly, Otub1 expression is gradually downregulated with increasing Tau-seeded Tau aggregation (Fig. S4a), which could be considered as a protective mechanism. PubMed:28083634

Appears in Networks:
Annotations
MeSH
Hippocampus

complex(p(HGNC:MAPT), p(HGNC:OTUB1)) hasComponent p(HGNC:OTUB1) View Subject | View Object

Appears in Networks:

Out-Edges 21

p(HGNC:OTUB1) decreases p(HGNC:MAPT, pmod(Ub)) View Subject | View Object

We focused particularly on Tau deubiquitination and identified three major candidate deubiquitinating enzymes, including Otub1, USP5, and USP9x, with Otub1 as the strongest Tau interactor according to statistical analysis PubMed:28083634

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p(HGNC:OTUB1) hasVariant p(HGNC:OTUB1, frag("?")) View Subject | View Object

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p(HGNC:OTUB1) hasVariant p(HGNC:OTUB1, var("p.Cys91Ala")) View Subject | View Object

Appears in Networks:

p(HGNC:OTUB1) increases complex(p(HGNC:MAPT), p(HGNC:OTUB1)) View Subject | View Object

We focused particularly on Tau deubiquitination and identified three major candidate deubiquitinating enzymes, including Otub1, USP5, and USP9x, with Otub1 as the strongest Tau interactor according to statistical analysis PubMed:28083634

Appears in Networks:

p(HGNC:OTUB1) increases complex(p(HGNC:MAPT), p(HGNC:OTUB1)) View Subject | View Object

Since Otub1 interacts with Tau and promotes phosphorylated and aggregated Tau levels in primary neurons, we hypothesized that Otub1 could act as a Tau deubiquitinase, interfering with pathological Tau degradation and hence Tau aggregation. PubMed:28083634

Appears in Networks:

p(HGNC:OTUB1) increases a(HBP:"Tau aggregates") View Subject | View Object

Expression of the candidate deubiquitinases Otub1, USP5, and USP9x in this assay demonstrated significantly increased Tau aggregation following expression of Otub1 (Fig. 2a; Fig. S3), not observed following expression of USP5 or USP9x (Fig. S3). PubMed:28083634

Appears in Networks:

p(HGNC:OTUB1) increases a(HBP:"Tau aggregates") View Subject | View Object

Endogenous Otub1 depletion significantly inhibited Tau aggregation, with the level of inhibition correlating with the level of knockdown efficiency,while use of a control siRNA did not affect levels of Otub1 nor aggregation efficiency (Fig. 2b). PubMed:28083634

Appears in Networks:

p(HGNC:OTUB1) increases a(HBP:"Tau aggregates") View Subject | View Object

Taken together, our data indicate that Otub1, a deubiquitinating enzyme, is a novel positive regulator of Tau aggregation and Tau stability in vitro, in a nonneuronal cell line. PubMed:28083634

Appears in Networks:

p(HGNC:OTUB1) increases a(HBP:"Tau aggregates") View Subject | View Object

Otub1 expression strikingly enhanced detergent-resistant AT8-positive Tau accumulation compared with GFP-infected neurons (Fig. 4b), indicating that Otub1 increased Tau-seeded Tau aggregation in primary neurons, corroborating the results obtained in a nonneuronal cell line. PubMed:28083634

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:OTUB1) negativeCorrelation a(HBP:"Tau aggregates") View Subject | View Object

Interestingly, Otub1 expression is gradually downregulated with increasing Tau-seeded Tau aggregation (Fig. S4a), which could be considered as a protective mechanism. PubMed:28083634

Appears in Networks:
Annotations
MeSH
Hippocampus

p(HGNC:OTUB1) regulates p(HGNC:MAPT) View Subject | View Object

Taken together, our data indicate that Otub1, a deubiquitinating enzyme, is a novel positive regulator of Tau aggregation and Tau stability in vitro, in a nonneuronal cell line. PubMed:28083634

Appears in Networks:

p(HGNC:OTUB1) increases p(HGNC:MAPT) View Subject | View Object

Otub1 also significantly increased total Tau protein level compared with GFP control (Fig. 3b). PubMed:28083634

Appears in Networks:

p(HGNC:OTUB1) decreases deg(p(HGNC:MAPT)) View Subject | View Object

We found that Tau degradation was significantly impaired in primary neurons infected with Otub1 WT, but not with catalytically dead mutant C91A, compared with GFP control. PubMed:28083634

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p(HGNC:OTUB1) regulates deg(p(HGNC:MAPT)) View Subject | View Object

These results indicate that Otub1 regulates Tau degradation, dependent on its catalytic activity (Fig. 5c). PubMed:28083634

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p(HGNC:OTUB1) decreases p(HGNC:MAPT, pmod(Ph, Ser, 202), pmod(Ph, Thr, 205)) View Subject | View Object

Immunocytological analysis with AT8 antibody against phosphorylated Tau (Ser202/Thr205) demonstrated that Otub1 expression drastically increased phospho-Tau (p-Tau Ser202/Thr205) in primary neurons compared with GFP expression (Fig. 3a). PubMed:28083634

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:OTUB1) decreases p(HGNC:MAPT, pmod(Ph, Ser, 202), pmod(Ph, Thr, 205)) View Subject | View Object

Biochemical analysis confirmed a sharp increase of phosphorylated Tau at Ser202/Thr205 in Otub1-infected primary neurons (Fig. 3b). PubMed:28083634

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:OTUB1) increases p(HGNC:MAPT, pmod(Ph, Ser, 202), pmod(Ph, Thr, 205)) View Subject | View Object

AAV-driven expression of Otub1-C91A did not increase AT8-positive Tau, in contrast to expression of wild-type Otub1 and the N-terminally truncated form of Otub1. This was demonstrated by immunofluorescence staining (Fig. 6a) and confirmed by biochemical analysis (Fig. 6b). PubMed:28083634

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p(HGNC:OTUB1) increases a(HBP:"Tau oligomers") View Subject | View Object

This revealed a significant increase of oligomeric Tau forms in AAV– Otub1-infected neurons compared with AAV–GFP-infected neurons (Fig. 4c). PubMed:28083634

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:OTUB1) increases a(HBP:"Tau oligomers") View Subject | View Object

The induction of oligomeric Tau forms was further confirmed using dot-blot analysis with T22 antibody (Fig. 4d), revealing a significant increase in oligomeric Tau following expression of Otub1. PubMed:28083634

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p(HGNC:OTUB1) decreases p(HGNC:MAPT, pmod(UbK48)) View Subject | View Object

Otub1 displayed strong preference for disassembling Lys48-linked polyubiquitin chains, while leaving Lys63-linked polyubiquitin chains unaffected (Fig. 5a). PubMed:28083634

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p(HGNC:OTUB1) causesNoChange p(HGNC:MAPT, pmod(UbK63)) View Subject | View Object

Otub1 displayed strong preference for disassembling Lys48-linked polyubiquitin chains, while leaving Lys63-linked polyubiquitin chains unaffected (Fig. 5a). PubMed:28083634

Appears in Networks:

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.