bp(GO:"protein ubiquitination")
E3s catalyze the last step in the conjugation process: covalent attachment of ubiquitin to the substrate. PubMed:14556719
In some other cases, the first ubiquitin moiety is conjugated to the substrate by one E3, while chain elongation is catalyzed by a different ligase, often termed E4 PubMed:14556719
It has been reported recently that while the monomeric form of UCH-L1 catalyzes deubiquitination, the dimers display a ubiquitin ligase activity that generates ubiquitin-K63 bonds (Liu et al., 2002). PubMed:14556719
For example, in the case of IkBalpha,the inhibitor of the transcriptional regulator NF-kB, modification by SUMO-1 was shown to protect the substrate from ubiquitination PubMed:14556719
Because Bag6 interacts with both E3 ligases as well as the proteasome [57,58,60], it may promote both the ubiquitination and delivery of misfolded proteins to the proteasome while preventing their aggregation PubMed:24457024
Finally, the E3 ubiquitin ligase binds to both the E2-bound ubiquitin and the protein substrate, promoting the transfer of ubiquitin onto the substrate PubMed:24457024
These studies demonstrated that both E2s and E3s can affect the conformation of the ubiquitin on the E2 surface to promote its transfer to the substrate PubMed:24457024
However, earlier biochemical investigations on the SCF (Skp, Cullin, F-box containing) ubiquitin ligase complex, the archetypal member of the cullin–RING ligases, indicated that E3s can also positively influence the rate of ubiquitin transfer from the E2 to the protein substrate [17,18]. PubMed:24457024
These studies demonstrated that both E2s and E3s can affect the conformation of the ubiquitin on the E2 surface to promote its transfer to the substrate PubMed:24457024
Some E3s can also stabilize the conformation between ubiquitin and the E2, thereby accelerating further the rate of conjugation of ubiquitin to proteins PubMed:24457024
Because Bag6 interacts with both E3 ligases as well as the proteasome [57,58,60], it may promote both the ubiquitination and delivery of misfolded proteins to the proteasome while preventing their aggregation PubMed:24457024
Cdc48/p97 generally acts downstream of ubiquitin ligases, although its activity may also promote ubiquitination in some cases; a major challenge is to delineate further the mechanism of action of this multipurpose enzyme PubMed:24457024
For example, BAG-2 inhibits client ubiquitination by CHIP by interfering with the interaction between CHIP and E2 ubiquitin-conjugating enzymes [148]. PubMed:21882945
For example, BAG-2 inhibits client ubiquitination by CHIP by interfering with the interaction between CHIP and E2 ubiquitin-conjugating enzymes [148]. PubMed:21882945
For example, Hsp70 and Hsp90 cooperate with the U-box-dependent ubiquitin ligase CHIP (C terminus of Hsc70-interacting protein) and a variety of other cofactors (such as BAG1 and BAG3) to ubiquitinate client proteins (23, 86, 198). PubMed:23746257
This model is consistent with an older study showing that inactivation of the ubiquitin-activating enzyme E1 leads to a defect in autolysosomal degradation and to an absence of ubiquitin-positive proteins within lysosomes [68]. PubMed:18930136
In cells that are exposed to stressors such as starvation or UPS inhibition, Alfy relocalizes from the nuclear envelope to filamentous cytoplasmic structures that are near autophagic membranes and ubiquitinated protein inclusions, as well as within autophagosomes [77]. PubMed:18930136
Similarly, a dramatic elevation of ubiquitinated substrates (from 4.2±0.1 to 37±1) upon epoxomicin treatment was detected in dendrites containing MAPT (compare Fig. S4E and Fig. S4F). PubMed:30145931
Similarly, a dramatic elevation of ubiquitinated substrates (from 4.2±0.1 to 37±1) upon epoxomicin treatment was detected in dendrites containing MAPT (compare Fig. S4E and Fig. S4F). PubMed:30145931
In many of these cases, the modification leads to targeting of the tagged substrate for degradation in the lysosome/vacuole PubMed:14556719
In many of these cases, the modification leads to targeting of the tagged substrate for degradation in the lysosome/vacuole PubMed:14556719
The UPS can be regulated at the level of ubiquitination or at the level of proteasome activity PubMed:14556719
The process of autophagy is controlled by parallel activation cascades that involve ubiquitin-like (UBL) protein modification, strikingly similar to the activation cascade that regulates the UPS (Figure 2a). PubMed:18930136
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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.