p(HGNC:MAPT, pmod(Ub))

Entity

Name

MAPT

Namespace

hgnc

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Not surprisingly, if recombinant tau is incubated with isolated 20S proteasomal complexes, degradation occurs (65). In this system proteolysis is bidirectional. Also, if tau is first ubiquitylated in an in vitro reaction and then incubated with isolated 26S proteasomes supplemented with MgCl2 and ATP, degradation proceeds (66). These data indicate tau can be a substrate for both forms of the proteasome. PubMed:24027553

For example, if HEK cells are transfected with tau and ubiquitin, tau is readily ubiquitylated and degraded by the proteasome (66). PubMed:24027553

For example, if HEK cells are transfected with tau and ubiquitin, tau is readily ubiquitylated and degraded by the proteasome (66). PubMed:24027553

However, another study, also using HEK cells and ubiquitin K48 and K63 mutants, demonstrated that in the presence of the E3 ligase CHIP, tau could be ubiquitylated by both K48 and K63 linkages (100). The likelihood that in vivo tau can be ubiquitylated in multiple ways is supported by studies showing tau isolated from NFTs in human brain has several forms of ubiquitin linkages as well as mono-ubiquitylation (101, 102). These data suggest that the physical structure of the ubiquitin chain is unlikely to be a sufficient signal for selectively targeting tau to either the proteasome or autophagy. PubMed:24027553

However, another study, also using HEK cells and ubiquitin K48 and K63 mutants, demonstrated that in the presence of the E3 ligase CHIP, tau could be ubiquitylated by both K48 and K63 linkages (100). The likelihood that in vivo tau can be ubiquitylated in multiple ways is supported by studies showing tau isolated from NFTs in human brain has several forms of ubiquitin linkages as well as mono-ubiquitylation (101, 102). These data suggest that the physical structure of the ubiquitin chain is unlikely to be a sufficient signal for selectively targeting tau to either the proteasome or autophagy. PubMed:24027553

These data indicated that phosphorylation of PP2A dephosphorylation sites is an important recognition signal for ubiquitination. We used 200 μg of amino-terminal His-tagged full-length recombinant human tau in an in vitro phosphorylation reaction with GSK-3Beta. When phosphorylated, the tau protein reacted on immunoblots with PHF1 (25, 26) and AT8 (24), indicating that at least sites Ser202, Thr205, Ser396, and Ser404 were phosphorylated. Following GSK-3Beta incubation, this tau served as an excellent substrate for in vitro ubiquitination using UbcH5B and the cofactor fraction from AD tau immunoprecipitates (Fig. 2a). This finding suggested that GSK-3Beta can place phosphates on tau that create recognition sites for an E3 Ub ligase. PubMed:14612456

These data suggest a model by which phosphorylated tau is bound to a chaperone and the complex is recognized by the E3 Ub ligase CHIP. We further examined whether recombinant GST-CHIP ubiquitinates phosphorylated tau in vitro in the presence of UbcH5B and Hsc70. Ubiquitination of phosphorylated tau was detected as high molecular weight bands by immunoblotting with 5E2 in the presence of UbcH5B and Hsc70 (Fig. 2e). PubMed:14612456

This result strongly suggested that the E2 conjugating enzyme for tau ubiquitination is UbcH5B. PubMed:14612456

The ubiquitin-targeted protein was identified as tau in paired helical filaments, and the conjugation sites were localized to the microtubule-binding region. PubMed:8391280

Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and β-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation. PubMed:25378699

We show that axotrophin/MARCH7, a RING-variant domain containing protein with similarity to E3 ubiquitin ligases interacts with tau. We find here that tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain, which diminishes its microtubule-binding. Tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain reducing microtubule-binding. PubMed:24905733

As reported in Table 6, several brain-derived proteins associated with the ACR bait were ubiquitinated. These proteins can be separated into four groups as follows: (a) group 1, proteins of the ubiquitin-conjugating system; (b) group 2, presynaptic proteins; (c) group 3, other proteins implicated in AD; and (d) group 4, phosphorylation-dependent ACR interactors. PubMed:27325702

Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and β-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation. PubMed:25378699

We show that axotrophin/MARCH7, a RING-variant domain containing protein with similarity to E3 ubiquitin ligases interacts with tau. We find here that tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain, which diminishes its microtubule-binding. Tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain reducing microtubule-binding. PubMed:24905733

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

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

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

In AD, tau is ubiquitinated, in Parkinson’s disease and dementia with Lewy bodies, it is a-synuclein, and in ALS and FTLD-U, it is TDP-43 PubMed:22908190

Tau is known to be ubiquitylated through Lys48 linkages by CHIP for proteasomal degradation PubMed:26631930

However, another study, also using HEK cells and ubiquitin K48 and K63 mutants, demonstrated that in the presence of the E3 ligase CHIP, tau could be ubiquitylated by both K48 and K63 linkages (100). The likelihood that in vivo tau can be ubiquitylated in multiple ways is supported by studies showing tau isolated from NFTs in human brain has several forms of ubiquitin linkages as well as mono-ubiquitylation (101, 102). These data suggest that the physical structure of the ubiquitin chain is unlikely to be a sufficient signal for selectively targeting tau to either the proteasome or autophagy. PubMed:24027553

This result strongly suggested that the E2 conjugating enzyme for tau ubiquitination is UbcH5B. PubMed:14612456

These data indicated that phosphorylation of PP2A dephosphorylation sites is an important recognition signal for ubiquitination. We used 200 μg of amino-terminal His-tagged full-length recombinant human tau in an in vitro phosphorylation reaction with GSK-3Beta. When phosphorylated, the tau protein reacted on immunoblots with PHF1 (25, 26) and AT8 (24), indicating that at least sites Ser202, Thr205, Ser396, and Ser404 were phosphorylated. Following GSK-3Beta incubation, this tau served as an excellent substrate for in vitro ubiquitination using UbcH5B and the cofactor fraction from AD tau immunoprecipitates (Fig. 2a). This finding suggested that GSK-3Beta can place phosphates on tau that create recognition sites for an E3 Ub ligase. PubMed:14612456

The ubiquitin-targeted protein was identified as tau in paired helical filaments, and the conjugation sites were localized to the microtubule-binding region. PubMed:8391280

Furthermore, the enhanced SUMO-immunoreactivity, costained with the hyperphosphorylated tau, is detected in cerebral cortex of the AD brains, and β-amyloid exposure of rat primary hippocampal neurons induces a dose-dependent SUMOylation of the hyperphosphorylated tau. Our findings suggest that tau SUMOylation reciprocally stimulates its phosphorylation and inhibits the ubiquitination-mediated tau degradation, which provides a new insight into the AD-like tau accumulation. PubMed:25378699

We show that axotrophin/MARCH7, a RING-variant domain containing protein with similarity to E3 ubiquitin ligases interacts with tau. We find here that tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain, which diminishes its microtubule-binding. Tau becomes mono-ubiquitinated by recombinant tau-interacting RING-variant domain reducing microtubule-binding. PubMed:24905733

In AD, tau is ubiquitinated, in Parkinson’s disease and dementia with Lewy bodies, it is a-synuclein, and in ALS and FTLD-U, it is TDP-43 PubMed:22908190