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Appears in Networks 2

In-Edges 5

composite(p(HGNC:MAPT, pmod(Ac, Lys, 163)), p(HGNC:MAPT, pmod(Ac, Lys, 280)), p(HGNC:MAPT, pmod(Ac, Lys, 281)), p(HGNC:MAPT, pmod(Ac, Lys, 369))) association p(HGNC:MAPT, pmod(Ac, Lys, 281)) View Subject | View Object

We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo. PubMed:28855586

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act(p(HGNC:EP300)) increases p(HGNC:MAPT, pmod(Ac, Lys, 281)) View Subject | View Object

Incubation with p300, not pCAF, led to tau acetylation, while both p300 and pCAF were active in transferring acetyl groups to histones as expected (Figure 1A). A few putative acetylated lysines were in the N- and C- terminal regions; 13 were in microtubule-binding domains (Figure 1B and Table-S1). Putative acetylated N-terminal lysines (e.g., lysines 163, 174, and 180) appeared to be acetylated in all MS analyses. Those in the microtubule-binding domains appeared to be acetylated in a subset of MS analyses, suggesting variable acetylation at these sites in vitro. PubMed:20869593

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 281)) decreases deg(p(HGNC:MAPT, pmod(Ac, Lys, 281))) View Subject | View Object

Depending on the sites, the acetylation of tau could inhibit its degradation (for example, when at Lys163, Lys280, Lys281 or Lys369) or, by contrast, facilitate its degradation and suppress its phosphorylation and aggregation (for example, when at Lys259, Lys290, Lys321 or Lys353) PubMed:26631930

Out-Edges 7

p(HGNC:MAPT, pmod(Ac, Lys, 281)) association composite(p(HGNC:MAPT, pmod(Ac, Lys, 163)), p(HGNC:MAPT, pmod(Ac, Lys, 280)), p(HGNC:MAPT, pmod(Ac, Lys, 281)), p(HGNC:MAPT, pmod(Ac, Lys, 369))) View Subject | View Object

We have used a knock-out/knock-in strategy in Drosophila to generate a strain with hTau inserted into the endogenous fly tau locus and expressed under the control of the endogenous fly tau promoter, thus avoiding potential toxicity due to genetic over-expression. hTau knock-in (KI) proteins were expressed at normal, endogenous levels, bound to fly microtubules and were post-translationally modified, hence displaying physiological properties. We used this new model to investigate the effects of acetylation on hTau toxicity in vivo. The simultaneous pseudo-acetylation of hTau at lysines 163, 280, 281 and 369 drastically decreased hTau phosphorylation and significantly reduced its binding to microtubules in vivo. These molecular alterations were associated with ameliorated amyloid beta toxicity. Our results indicate acetylation of hTau on multiple sites regulates its biology and ameliorates amyloid beta toxicity in vivo. PubMed:28855586

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 281)) decreases p(HGNC:MAPT, pmod(Ph, Thr, 205)) View Subject | View Object

Surprisingly, we show that tau acetylation alters phosphorylation at residues S202/T205 (comprising the AT8 epitope), indicating acetylation-dephosphorylation cross-talk. Using a series of biochemical approaches, we found that K280/K281 acetylation impaired tau-mediated MT assembly function and also significantly enhanced tau aggregation. We also demonstrate that methylene blue, a reported tau aggregation inhibitor, modulates tau acetylation, a novel mechanism of action for this class of compounds PubMed:28287136

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 281)) increases a(HBP:"Tau aggregates") View Subject | View Object

Surprisingly, we show that tau acetylation alters phosphorylation at residues S202/T205 (comprising the AT8 epitope), indicating acetylation-dephosphorylation cross-talk. Using a series of biochemical approaches, we found that K280/K281 acetylation impaired tau-mediated MT assembly function and also significantly enhanced tau aggregation. We also demonstrate that methylene blue, a reported tau aggregation inhibitor, modulates tau acetylation, a novel mechanism of action for this class of compounds PubMed:28287136

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 281)) decreases p(HGNC:WWC1) View Subject | View Object

Here we report abnormal acetylation of K274 and K281 on tau, identified in AD brains, promotes memory loss and disrupts synaptic plasticity by reducing postsynaptic KIdney/BRAin (KIBRA) protein, a memory-associated protein.Transgenic mice expressing human tau with lysine-to-glutamine mutations to mimic K274 and K281 acetylation (tauKQ) exhibit AD-related memory deficits and impaired hippocampal long-term potentiation (LTP). TauKQ reduces synaptic KIBRA levels and disrupts activity-induced postsynaptic actin remodeling and AMPA receptor insertion. The LTP deficit was rescued by promoting actin polymerization or by KIBRA expression. In AD patients with dementia, we found enhanced tau acetylation is linked to loss of KIBRA. PubMed:27041503

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 281)) decreases bp(GO:"actin filament polymerization") View Subject | View Object

Here we report abnormal acetylation of K274 and K281 on tau, identified in AD brains, promotes memory loss and disrupts synaptic plasticity by reducing postsynaptic KIdney/BRAin (KIBRA) protein, a memory-associated protein.Transgenic mice expressing human tau with lysine-to-glutamine mutations to mimic K274 and K281 acetylation (tauKQ) exhibit AD-related memory deficits and impaired hippocampal long-term potentiation (LTP). TauKQ reduces synaptic KIBRA levels and disrupts activity-induced postsynaptic actin remodeling and AMPA receptor insertion. The LTP deficit was rescued by promoting actin polymerization or by KIBRA expression. In AD patients with dementia, we found enhanced tau acetylation is linked to loss of KIBRA. PubMed:27041503

Appears in Networks:

p(HGNC:MAPT, pmod(Ac, Lys, 281)) decreases deg(p(HGNC:MAPT, pmod(Ac, Lys, 281))) View Subject | View Object

Depending on the sites, the acetylation of tau could inhibit its degradation (for example, when at Lys163, Lys280, Lys281 or Lys369) or, by contrast, facilitate its degradation and suppress its phosphorylation and aggregation (for example, when at Lys259, Lys290, Lys321 or Lys353) PubMed:26631930

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.