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Based on my research and analysis of the provided GO-CAM model (gomodel:6348a65d00002236), I'll now provide a comprehensive review of this model from a GO-CAM curation perspective.

Review of GO-CAM Model: "USP44-mediated deubiquitination of CDC20 controlling anaphase initiation (Human)"

Model Overview

This model (gomodel:6348a65d00002236) represents the regulation of anaphase initiation through USP44-mediated deubiquitination of CDC20 in human cells. The model captures the interactions between four key proteins:

  1. USP44 (UniProtKB:Q9H0E7) - A deubiquitinating enzyme
  2. CDC20 (UniProtKB:Q12834) - A cell division cycle protein and APC/C co-activator
  3. UBE2C (UniProtKB:O00762) - A ubiquitin-conjugating enzyme
  4. ANAPC11 (UniProtKB:Q9NYG5) - An anaphase-promoting complex subunit

Biological Context

This model captures the molecular mechanisms of the spindle assembly checkpoint, which ensures proper chromosome segregation during mitosis. Specifically:

  1. UBE2C has ubiquitin conjugating enzyme activity that positively regulates CDC20's function
  2. USP44 has deubiquitinase activity that negatively regulates CDC20's function
  3. CDC20 has APC-binding activity which positively affects ANAPC11's function
  4. ANAPC11 has ubiquitin-protein transferase activity

Together, these activities represent a regulatory circuit of ubiquitination and deubiquitination that controls the metaphase-to-anaphase transition in mitosis.

Model Evaluation

Strengths

  1. Accurate Biological Representation: The model accurately captures the key proteins involved in anaphase initiation control through CDC20 regulation, supported by the PMID:17443180 (Stegmeier et al.) which shows that USP44 deubiquitinates CDC20.

  2. Appropriate Causal Relations: The model correctly uses RO:0002304 (causally upstream of, positive effect) and RO:0002630 (directly negatively regulates) to represent the relationships between activities.

  3. Clear Cellular Localization: All activities are appropriately annotated with cellular compartments (GO:0005680 for anaphase-promoting complex, GO:0072686 for mitotic spindle).

  4. Proper Evidence Codes: The model uses appropriate evidence codes like ECO:0000314 (direct assay evidence) with corresponding PMID references.

Areas for Improvement

  1. Redundant Causal Association: There appear to be two identical causal associations from USP44's deubiquitinase activity to CDC20's activity, both using the same predicate (RO:0002630). One of these lacks evidence while the other cites PMID:17443180. The redundant association without evidence should be removed.

  2. Missing Evidence for One Connection: The causal association between CDC20's APC binding activity (gomodel:6348a65d00002236/6348a65d00002247) and ANAPC11's ubiquitin-protein transferase activity lacks evidence (empty evidence array).

  3. Could Benefit from Additional Context: While the model accurately captures the core regulatory mechanism, it could be enhanced by including additional proteins involved in this pathway, such as MAD2L1, which is known to form a complex with CDC20 as described in the referenced paper.

  4. No Transport or Input Activities: The model doesn't include any chemical entities or transport activities that could provide additional contextual information about the process.

Biological Accuracy

The model is biologically accurate and supported by the literature. The Stegmeier et al. paper (PMID:17443180) clearly demonstrates:

  1. USP44 is a deubiquitinating enzyme critical for spindle checkpoint function
  2. USP44 prevents premature activation of APC/C by deubiquitinating CDC20
  3. USP44 helps stabilize the inhibitory MAD2-CDC20 complex
  4. There's a dynamic balance between ubiquitination and deubiquitination in regulating anaphase entry

The GO-CAM model accurately represents these findings, though it doesn't capture the full complexity of the MAD2-CDC20 interaction described in the paper.

GO-CAM Best Practices Compliance

Reviewing against GO-CAM best practices:

  1. Complex Annotation: The model follows best practices by representing individual protein activities rather than annotating to complexes (as per "How_to_annotate_complexes_in_GO-CAM").

  2. Regulation Representation: The model correctly represents regulation by using appropriate causal relationships between activities, following the guidelines in "Regulation and Regulatory Processes in GO-CAM".

  3. Part_of Relations: Each molecular function is appropriately annotated as part_of a biological process (GO:0045841 and GO:0045842).

  4. Cellular Context: All activities include occurs_in annotations to provide cellular context.

Recommendations

  1. Remove Redundant Causal Association: Delete the USP44's negative regulation of CDC20 that lacks evidence.

  2. Add Evidence for Missing Connection: Add evidence for the causal association between CDC20 and ANAPC11.

  3. Consider Expanding the Model: Include MAD2L1 and its interaction with CDC20 to better represent the full regulatory mechanism described in the paper.

  4. Add Chemical Entity: Consider adding ubiquitin as a chemical entity to provide more context to the ubiquitination/deubiquitination processes.

  5. Clarify UBE2C's Role: The evidence for UBE2C's role (PMID:12629039) could not be accessed, so verifying this relationship with alternative evidence might be beneficial.

Conclusion

Overall, this is a well-constructed GO-CAM model that accurately represents the key molecular mechanisms involved in USP44-mediated regulation of anaphase initiation through CDC20 deubiquitination. With a few minor improvements, it would be an excellent representation of this biological process.

The model follows most GO-CAM best practices and is supported by high-quality experimental evidence from the literature. The main suggestion for improvement is to remove redundant relationships and potentially expand the model to include additional relevant proteins like MAD2L1 for a more comprehensive representation of the regulatory network.