IndraLab

Statements

OTUB1 activates MAPT. 12 / 12
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"Consequently, Otub1 dependent deubiquitination inhibits Tau degradation through the proteasome pathway and prolongs its half-life, leading to accumulation of pathological forms of Tau."
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"Otub1 increases Tau stability and increases Tau aggregation in a well characterized cellular Tau aggregation model."
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"Knockdown of Otub1 increased Tau turnover, correlating with the decrease in expression of Otub1 obtained by the different siRNAs."
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"Otub1 but not Otub1-C91A impairs Tau degradation by removing Lys48 linked polyubiquitin chains from Tau in primary neurons."
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"Finally, we demonstrated that expression of Otub1 but not its catalytically inactive form induced pathological Tau forms after 2months in Tau transgenic mice invivo, including AT8 positive Tau and oligomeric Tau forms."
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"In addition, we found robust induction of a (homo- or heterotypic) Tau complex (Tau c), which was strongly detected in AAV-Otub1-infected neurons but absent in AAV-GFP-infected neurons, indicating clearcut Otub1 induced modulation of Tau in neurons."
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"Otub1 strongly increased AT8 positive Tau and oligomeric Tau forms and increased Tau seeded Tau aggregation in primary neurons."
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"Otub1 enhances Tau oligomerization and Tau seeded Tau aggregation in primary neurons."
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"Taken together, our data demonstrate that Otub1, identified as a Tau interacting protein in the Tau interactome mapping, modulates Tau, by increasing Tau seeded Tau aggregation, by formation of a Otub1 induced Tau complex Tau c, and by increasing the concentration of oligomeric Tau forms in primary neurons."
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"Taken together, we conclude that overexpressed Otub1 in primary neurons expressing TauP301S increased total Tau and induced a robust increase in AT8 positive Tau."
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"We demonstrate that Otub1 regulates levels of Lys48 linked ubiquitin conjugated Tau and increases pathological forms of Tau invitro and invivo."
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"Otub1 expression strikingly enhanced detergent resistant AT8 positive Tau accumulation compared with GFP infected neurons, indicating that Otub1 increased Tau seeded Tau aggregation in primary neurons, corroborating the results obtained in a nonneuronal cell line."
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