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Based on my research and the model details, I'll now provide a comprehensive review of the GO-CAM model gomodel:653b0ce600000432.

Review of GO-CAM Model gomodel:653b0ce600000432

Model Information

  • ID: gomodel:653b0ce600000432
  • Title: TRIM32-TAX1BP1-dependent selective autophagic degradation of TICAM1 (Human)
  • Taxon: Human (NCBITaxon:9606)
  • Status: Production

Overview of the Model

This model represents a signaling pathway involving the TLR4 receptor, adaptors TICAM2 and TICAM1 (TRIF), the negative regulator complex of TRIM32-TAX1BP1, and the DNA-binding transcription factor activity of IRF3. The model describes a mechanism for negatively regulating TLR3/4-mediated immune responses by targeting TICAM1 for selective autophagic degradation.

Biological Content Assessment

The model captures a key regulatory mechanism in TLR3/4 signaling as described in the literature, particularly in the paper by Yang et al. (2017, PMID:28898289). The model accurately represents:

  1. TLR4 receptor activity recruiting TICAM2
  2. TICAM2 acting as a molecular adaptor that directly positively regulates TICAM1
  3. TICAM1 molecular adaptor activity
  4. TAX1BP1 protein-macromolecule adaptor activity targeting TICAM1 for autophagic degradation
  5. TRIM32 protein-macromolecule adaptor activity providing input for TAX1BP1
  6. IRF3 DNA-binding transcription factor activity as a downstream effector

Causal Connections Assessment

The causal connections in the model are appropriate and consistent with the literature:

  1. TLR4 signaling receptor activity → directly positively regulates → TICAM2 molecular adaptor activity
  2. TICAM2 molecular adaptor activity → directly positively regulates → TICAM1 molecular adaptor activity
  3. TRIM32 protein-macromolecule adaptor activity → provides input for → TAX1BP1 protein-macromolecule adaptor activity
  4. TAX1BP1 protein-macromolecule adaptor activity → regulates autophagosome assembly → TICAM1 molecular adaptor activity

These causal connections accurately reflect the mechanism described in the literature, where TRIM32 acts as a bridge protein that connects TICAM1 to TAX1BP1, leading to selective autophagic degradation of TICAM1 and termination of TLR3/4 signaling.

GO-CAM Best Practice Compliance

The model largely follows GO-CAM best practices:

  1. Molecular Adaptor Annotation: The model correctly uses GO:0060090 (molecular adaptor activity) for TICAM2 and TICAM1, and GO:0030674 (protein-macromolecule adaptor activity) for TAX1BP1 and TRIM32, consistent with the "How to annotate molecular adaptors" guidelines.

  2. Causal Relations: The use of "directly positively regulates" (RO:0002629) and "provides input for" (RO:0002413) is appropriate for the adaptor relationships described.

  3. Contextual Information: Each activity is properly annotated with cellular location (occurs_in) and biological process (part_of).

  4. Evidence Documentation: Evidence codes and PMIDs are properly included for almost all assertions.

Suggestions for Improvement

While the model is generally well-constructed, I have a few suggestions for improvement:

  1. Add Missing Evidence: The causal association between TICAM2 and TICAM1 lacks evidence (evidence field is empty). This should be supported with an appropriate PMID, likely PMID:18222170 which is used elsewhere in the model.

  2. Consider Additional Activities: The model could potentially be enriched by including:

  3. The downstream signaling components after TICAM1, such as TBK1 and its kinase activity
  4. The E3 ubiquitin ligase activity of TRIM32, although the paper indicates this function is E3-independent in this specific pathway

  5. LC3 (MAP1LC3A is listed in the objects but not included in the model activities)

  6. Clarify Mechanism: The relationship between TAX1BP1 and TICAM1 uses "RO:0002409" which is not one of the standard causal relations mentioned in the instructions (appears to be related to autophagy). Consider whether this should be explicitly documented or use a more standard relation with additional context.

Biological Accuracy

The model accurately represents the key findings from Yang et al. (2017) that TRIM32 negatively regulates TLR3/4-mediated innate immune responses by promoting selective autophagic degradation of TICAM1 through TAX1BP1. The biological content is consistent with:

  1. The interaction and functional relationships between all proteins involved
  2. The subcellular locations of the activities
  3. The relevant biological processes
  4. The human-specific nature of this pathway

Overall Assessment

This is a well-constructed GO-CAM model that effectively captures a significant regulatory mechanism in TLR3/4 signaling. It accurately represents the role of TRIM32 and TAX1BP1 in the selective autophagic degradation of TICAM1, providing a clear visualization of how this process negatively regulates TLR3/4-mediated innate immune responses.

The model is parsimonious, focusing on the key components and activities necessary to understand this regulatory mechanism. Minor improvements could be made by adding missing evidence and potentially expanding the model to include additional downstream components, but these are not critical issues.