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Based on the information retrieved, I'll now conduct a thorough review of the GO-CAM model with ID "64c3044100001787" titled "Inhibition of cGAS-STING signaling in the nucleus by BANF1 (Human)".

GO-CAM Model Review: "Inhibition of cGAS-STING signaling in the nucleus by BANF1 (Human)"

Model ID: gomodel:64c3044100001787

Summary of the Model

This GO-CAM model describes the inhibition of cGAS-STING signaling in the nucleus by the BANF1 protein in humans. The model focuses on a molecular mechanism where BANF1 restricts cGAS activity on nuclear DNA to prevent inappropriate innate immune activation, which could lead to autoimmunity. The pathway involves several key proteins:

  • BANF1 (Barrier-to-autointegration factor)
  • CGAS (Cyclic GMP-AMP synthase)
  • STING1 (Stimulator of interferon genes protein)

Key Activities and Connections in the Model

The model consists of several molecular activities connected by causal relationships:

  1. BANF1 (O75531) binds double-stranded DNA in the nucleus
  2. BANF1 directly positively regulates CGAS (Q8N884) inhibition
  3. CGAS binds double-stranded DNA in the nucleus and produces cGAMP
  4. CGAS provides input for condensate formation which contributes to STING1 activation
  5. STING1 (Q86WV6) binds cGAMP and transduces signals leading to interferon production

Biological Context

This model describes an important regulatory mechanism for innate immunity. The cGAS-STING pathway is a key sensor of cytosolic DNA that can trigger type I interferon responses. When nuclear DNA is exposed (e.g., during nuclear envelope breakdown), BANF1 prevents inappropriate activation of this pathway by outcompeting cGAS for binding to nuclear DNA.

Quality Control Assessment

Consistency with GO-CAM Best Practices

  1. Complex Annotation:
  2. The model correctly represents the individual activities of each protein rather than using complex IDs, since the specific activities of each protein are known.

  3. This approach aligns with the complex annotation guidelines from "How to annotate complexes in GO-CAM".

  4. Regulatory Processes:

  5. The model correctly uses the "directly positively regulates" relation (RO:0002629) to connect BANF1's DNA binding activity to CGAS inhibition.

  6. This follows the guidelines in "Regulation and Regulatory Processes in GO-CAM" where the regulatory mechanism is known and has a specific effect.

  7. Location Specification:

  8. Each activity appropriately includes location information (nucleus, ER membrane) which is critical for understanding the spatial organization of this pathway.

  9. Evidence Attribution:

  10. All activities are supported by appropriate experimental evidence from peer-reviewed literature.

Biological Accuracy

  1. BANF1 Function:
  2. The model correctly captures BANF1's role in binding to DNA (GO:0003690) in the nucleus and its inhibitory effect on cGAS.

  3. This is consistent with the literature that describes BANF1 as outcompeting cGAS for DNA binding.

  4. cGAS Activities:

  5. The model includes both cGAS's enzymatic activity (GO:0061501, 2',3'-cyclic GMP-AMP synthase activity) and its ability to form molecular condensates (GO:0140693).

  6. These activities are accurately represented as occurring in the nucleus.

  7. STING1 Activities:

  8. The model correctly depicts STING1's binding to cGAMP (GO:0061507) and signaling adaptor activity (GO:0035591) in the ER membrane.

  9. The causal relationships between STING1 activities are biologically accurate.

  10. Causal Flow:

  11. The flow of causal relationships in the model accurately represents the biological process:
    • BANF1 inhibits cGAS activity on nuclear DNA
    • cGAS produces cGAMP and forms condensates
    • STING1 binds cGAMP and activates downstream signaling

Areas for Improvement

  1. Temporal Aspects:

  2. The model could potentially benefit from additional information about when this inhibition is most critical (e.g., during mitosis or in response to certain cellular stresses).

  3. Downstream Effects:

  4. While the model focuses on the core regulatory mechanism, it could be expanded to include downstream effects of STING1 activation, such as TBK1 and IRF3 activation leading to interferon production.

  5. Cross-talk with Other Pathways:

  6. The model could be enhanced by including connections to other regulatory pathways that might influence this process.

Conclusion

The GO-CAM model "Inhibition of cGAS-STING signaling in the nucleus by BANF1 (Human)" is a well-constructed representation of this important regulatory mechanism. It adheres to GO-CAM best practices and accurately represents the biological process based on current scientific literature.

The model highlights a critical regulatory mechanism that prevents inappropriate activation of innate immune responses by self-DNA, which is essential for maintaining immune homeostasis. The specific activities of BANF1, cGAS, and STING1 are represented with appropriate molecular functions, locations, and causal relationships.

This model provides a valuable resource for understanding how cells distinguish between self and non-self DNA to properly regulate innate immune responses.