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Based on the information I have examined, I will now provide a comprehensive review of GO-CAM model gomodel:63f809ec00001734 titled "TGF-beta-mediated inhibition of TAF7 via TRIM26".

GO-CAM Review: TGF-beta-mediated inhibition of TAF7 via TRIM26 (gomodel:63f809ec00001734)

Overall Summary

This model represents a signaling pathway in which TGF-beta1 (TGFB1) signaling leads to inhibition of transcription through a cascade involving SMAD3, MYC, and TRIM26-mediated ubiquitination of TAF7. The model appears to be based primarily on findings from PMID:29203640, which demonstrated that TGF-beta induces growth arrest through TRIM26-dependent degradation of TAF7, with MYC antagonizing this process.

Biological Context and Pathway Logic

The model demonstrates how TGF-beta signaling can inhibit cell proliferation by downregulating transcription. The pathway follows this logical sequence: 1. TGFB1 cytokine activity initiates SMAD signaling 2. SMAD3 activates DNA-binding transcription factor activity 3. SMAD3 provides input for TRIM26 ubiquitin ligase activity 4. TRIM26 directly negatively regulates TAF7 5. TAF7 normally functions as an RNA polymerase II general transcription initiation factor 6. MYC antagonizes SMAD3 signaling through negative regulation

The model shows that MYC's transcription repressor activity opposes SMAD3 signaling in this pathway, which aligns with the findings from the literature that MYC antagonizes TGF-beta-induced proliferative arrest.

Technical Evaluation

Entity Annotation and Molecular Functions

The model includes five key activities involving different proteins:

  1. TGFB1 cytokine activity (GO:0005125)
  2. Enabled by TGFB1 (UniProtKB:P01137)
  3. Occurs in extracellular space (GO:0005615)

  4. Part of SMAD protein signal transduction (GO:0060395)

  5. DNA-binding transcription factor activity (GO:0003700)

  6. Enabled by SMAD3 (UniProtKB:P84022)
  7. Occurs in nucleus (GO:0005634)

  8. Part of SMAD protein signal transduction (GO:0060395)

  9. Ubiquitin protein ligase activity (GO:0061630)

  10. Enabled by TRIM26 (UniProtKB:Q12899)
  11. Occurs in nucleus (GO:0005634)

  12. Part of proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161)

  13. RNA polymerase II general transcription initiation factor activity (GO:0016251)

  14. Enabled by TAF7 (UniProtKB:Q15545)
  15. Occurs in nucleus (GO:0005634)

  16. Part of positive regulation of transcription by RNA polymerase II (GO:0045944)

  17. DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227)

  18. Enabled by MYC (UniProtKB:P01106)
  19. Occurs in nucleus (GO:0005634)
  20. Part of negative regulation of transcription initiation by RNA polymerase II (GO:0060633)

All entities have appropriate molecular functions, cellular components, and are placed within relevant biological processes.

Causal Relationships

The model uses three causal relationships: 1. TGFB1 provides input for (RO:0002407) SMAD3 2. SMAD3 provides input for (RO:0002407) TRIM26 3. TRIM26 directly negatively regulates (RO:0002630) TAF7 4. MYC regulates via a negative effect (RO:0012010) SMAD3

These causal relations appropriately capture the regulatory relationships described in the reference paper.

Improvement Suggestions

Based on GO-CAM best practices, I have the following recommendations:

  1. Evidence Citations: The evidence is primarily from a single paper (PMID:29203640), which is appropriate. However, additional supporting evidence for the core mechanisms could strengthen the model.

  2. Complex Representation: Currently the model does not represent any protein complexes. According to the "How to annotate complexes in GO-CAM" document, if specific activities are carried out by individual proteins within a complex (as is the case here), then representing them as separate entities is appropriate.

  3. Regulatory Process Representation: The model follows the guidelines for regulatory processes by showing specific mechanisms and capturing the negative regulatory effect of TRIM26 on TAF7.

  4. Additional Mechanistic Details: If available from the literature, the model could be enhanced by including:

  5. The specific E2 ubiquitin-conjugating enzyme that works with TRIM26
  6. The specific lysine residues on TAF7 that are ubiquitinated

  7. Additional downstream effects of TAF7 degradation

  8. Cell Type Context: Adding information about the specific cell types where this pathway has been demonstrated would enhance the biological context.

Conclusion

The GO-CAM model "TGF-beta-mediated inhibition of TAF7 via TRIM26" effectively captures a signaling pathway from TGF-beta through SMAD3 and TRIM26 to the negative regulation of TAF7, with antagonism by MYC. The model follows GO-CAM best practices for representing regulatory relationships and protein activities.

The model is well-constructed and represents the biological knowledge from the literature accurately. The entities have appropriate molecular function annotations, and the causal relationships between activities reflect our understanding of the pathway. Minor enhancements could be made to add more mechanistic details and cellular context, but overall, this is a high-quality GO-CAM model.