Skip to content

Based on the information gathered, I'll now review GO-CAM model gomodel:646ff70100005032.

Review of GO-CAM Model 646ff70100005032

Model Overview

Title: HCMV UL138 substains STAT1 activation during viral latency (Human-Cytomegalovirus)
ID: gomodel:646ff70100005032
Taxon: Human (NCBITaxon:9606)
Status: Production

Model Content Summary

This GO-CAM model represents how the Human Cytomegalovirus (HCMV) protein UL138 interacts with host proteins to sustain STAT1 activation during viral latency. The model consists of four key activities:

  1. UL138 (F5HGQ8) - Molecular adaptor activity providing input for WDR48/UAF1 activity
  2. WDR48/UAF1 (Q8TAF3) - Deubiquitinase activator activity directly positively regulating USP1 activity
  3. USP1 (O94782) - Cysteine-type deubiquitinase activity removing ubiquitin from substrates
  4. STAT1 (P42224) - DNA-binding transcription factor activity involved in cell surface receptor signaling via JAK-STAT

These activities function together in a pathway that promotes positive regulation of receptor signaling via JAK-STAT pathway (GO:0046427).

Biological Content Evaluation

The model accurately reflects the findings from the research paper (PMID:37289831), which demonstrates a mechanism by which HCMV UL138 protein interacts with host UAF1/WDR48 and USP1 to enhance and sustain STAT1 phosphorylation and activation during viral latency. The sustaining of STAT1 activation helps restrict viral replication during latency establishment.

Key findings from the research paper that are accurately represented in the model:

  1. UL138 interacts with WDR48/UAF1 and USP1
  2. This interaction enhances and sustains phosphorylated STAT1 (pSTAT1) levels
  3. The pathway contributes to positive regulation of JAK-STAT signaling
  4. This mechanism is important for establishing viral latency

Model Structure and Connections Evaluation

The causal connections in the model are appropriate and follow GO-CAM best practices:

  1. UL138 (molecular adaptor activity) → RO:0002413 (provides input for) → WDR48/UAF1 (deubiquitinase activator activity)
  2. WDR48/UAF1 (deubiquitinase activator activity) → RO:0002629 (directly positively regulates) → USP1 (cysteine-type deubiquitinase activity)
  3. USP1 (cysteine-type deubiquitinase activity) → RO:0002407 (contributes to) → STAT1 (DNA-binding transcription factor activity)

All activities are appropriately contained within the same biological process: positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427).

Subcellular Localization Accuracy

The subcellular locations are accurately annotated: - UL138 in cytoplasm (GO:0005737) - WDR48/UAF1 activity in host Golgi membrane (GO:0044178) - USP1 in nucleus (GO:0005634) - STAT1 in nucleus (GO:0005634)

These localizations are consistent with the research findings where UL138 interacts with cytoplasmic or membrane-bound UAF1/WDR48, activating USP1, which ultimately affects STAT1 in the nucleus.

Evidence and References

The model is well-supported with appropriate evidence codes and literature references:

  • ECO:0000314 (direct assay evidence used in manual assertion) is used throughout
  • Primary references include PMID:37289831, PMID:18082604, PMID:18032488, PMID:10973496, and PMID:11972023
  • All proteins are identified with their UniProt accessions

Suggested Improvements

While this model is well-constructed, a few adjustments could improve its completeness:

  1. Clarify the intermediate step: The model could more clearly show how USP1's deubiquitinase activity leads to sustained STAT1 activity. The paper suggests this mechanism is independent of TBK1 stabilization (unlike what was previously reported for USP1). This detail could make the model more informative.

  2. Refine causal relationship between USP1 and STAT1: The current relationship uses RO:0002407 (contributes to), but the research suggests this might more specifically be a positive regulatory relationship (RO:0002629 - directly positively regulates), as USP1 activity directly sustains STAT1 phosphorylation.

  3. Include STAT1 phosphorylation state: The model could potentially note that the specific active form of STAT1 is phosphorylated at tyrosine 701 (pSTAT1), which is a key aspect of the research findings.

  4. Consider adding viral context: While this is implied in the title, the model could more explicitly represent that this is occurring in the context of HCMV latent infection.

Conclusion

Overall, this GO-CAM model (gomodel:646ff70100005032) provides an accurate and well-structured representation of how HCMV UL138 protein interacts with host deubiquitination machinery to sustain STAT1 activation during viral latency. It is consistent with the research findings and follows GO-CAM best practices for modeling protein interactions and causal relationships.

The model effectively captures a complex host-virus interaction that contributes to viral latency, representing an elegant mechanism by which HCMV commandeers host cell processes for its long-term persistence. With the minor suggested improvements, this would be an even more valuable contribution to our understanding of HCMV latency mechanisms in GO-CAM format.