Proteomic Study Of The Ubiquitin E3 Ligase HUWE1 Interaction With Ubiquitin And ADP-Ribose Modified Proteins
Bibliographic record
Abstract
Ubiquitination and ADP-ribosylation are important post-translational modifications (PTMs), especially in cellular response to DNA damage. HECT, UBA, and WWE domain containing E3 ubiquitin protein ligase 1 (HUWE1) is an important ubiquitin E3 ligase involved in many cellular processes. HUWE1 contains regions involved in substrate interaction and domains for PTM recognition. Specifically, HUWE1 WWE and tandem ubiquitin-binding motif (tUBM) domains interact with ADPr/iso-ADPr and ubiquitin, respectively. However, the interaction between these domains and cellular ADP-ribose and ubiquitin and potentially substrate interactions are not well investigated. Thus, this project aimed to investigate the interactome of HUWE1 WWE and tUBM domain, focusing on their ability to bind proteins modified by mono-ADP-ribose (MAR)/poly-ADP-ribose (PAR) and ubiquitin using GST pulldown assay. First, using Western blot and confocal microscopy, distinct dynamics of ubiquitination and ADP-ribosylation were observed in response to different DNA damage treatments. Second, the study demonstrated that the WWE-tUBM domain interacts with both cellular ADP-ribose and ubiquitin. Moreover, through a proteomic approach using affinity mass spectrometry, this study identified novel proteins that interact with the WWE and tUBM domains following Ultraviolet (UV) induced DNA damage. Together, the findings of this project contribute to a better understanding of how HUWE1 engages with its substrates and highlight the role of WWE and tUBM domains and their ability to recognize PTMs in mediating these interactions.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".