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Now, after reviewing all the collected information, I'll provide a comprehensive review of gomodel:61e0e55600001295 (NLRP1 inflammasome leading to pyroptosis).

Review of GO-CAM model: NLRP1 inflammasome leading to pyroptosis (Human)

ID: gomodel:61e0e55600001295

1. Overview

This GO-CAM model represents the NLRP1 inflammasome pathway leading to pyroptosis in humans. The model captures key molecular activities, causal relationships, and cellular locations of components involved in NLRP1 inflammasome activation and the subsequent pyroptotic cell death process. The model is annotated with solid literature evidence and includes proper citation of relevant scientific papers.

2. Model Content Assessment

2.1 Biological Accuracy

The model correctly captures the essential components and mechanisms of NLRP1 inflammasome activation:

  • NLRP1 autolytic processing and activation: The model correctly represents NLRP1's requirement for autolytic cleavage within its FIIND domain (between F1212 and S1213), which is a prerequisite for inflammasome activation as demonstrated in PMID:22665479.
  • Dipeptidyl peptidase regulation: The model captures the interaction between DPP8/DPP9 and NLRP1, where DPP8/DPP9 negatively regulate NLRP1 (PMID:33731929), and inhibition of DPP8/DPP9 can trigger NLRP1 activation.
  • ASC recruitment: The model correctly shows NLRP1 recruiting ASC via its CARD domain, which is essential for NLRP1 inflammasome activity (PMID:22665479).
  • Caspase-1 activation: The model includes caspase-1 recruitment and activation, which leads to downstream gasdermin D cleavage.
  • Pyroptosis induction: The model properly represents the final outcome of NLRP1 inflammasome activation as pyroptotic cell death via Gasdermin D pore formation.

2.2 Adherence to GO-CAM Curation Standards

The model follows GO-CAM curation standards:

  • Proper GO term usage: The model uses appropriate GO molecular function (MF) terms for activities (e.g., GO:0140693 "molecular condensate scaffold activity", GO:0035591 "signaling adaptor activity").
  • Correct causal relations: The model correctly uses causal relationship predicates such as RO:0002629 "directly positively regulates" to connect activities.
  • Appropriate evidence codes: Assertions are supported by ECO:0000314 (direct assay evidence used in manual assertion) with proper PMID references.
  • Cellular component annotation: Activities are properly located in cellular components (e.g., cytosol GO:0005829).

2.3 Representation of Molecular Mechanisms

The model effectively represents key molecular mechanisms:

  1. NLRP1 double-stranded RNA binding (GO:0003725) in the cytosol, followed by pattern recognition receptor activity (GO:0038187), which are necessary for initial response to pathogens like viruses.

  2. NLRP1 molecular condensate scaffold activity (GO:0140693) that is required for inflammasome assembly.

  3. NLRP1 signaling adaptor activity (GO:0035591), which connects the initial sensing to downstream signaling.

  4. NLRP1 cysteine-type endopeptidase activator activity (GO:0140608), which enables the activation of Caspase-1.

  5. CASP1 cysteine-type endopeptidase activity (GO:0004197) leading to cleavage of gasdermin D.

  6. GSDMD wide pore channel activity (GO:0022829) in the plasma membrane, causing cell rupture and pyroptosis.

  7. Negative regulation of this pathway by dipeptidyl peptidases DPP8/DPP9 (GO:0008239).

3. Strengths of the Model

  1. Comprehensive representation: The model covers the complete pathway from initial NLRP1 sensing to final pyroptotic outcome.

  2. Strong literature support: Each activity and relationship is supported by high-quality published evidence with appropriate citations.

  3. Molecular detail: The model captures important molecular details such as the autolytic cleavage of NLRP1 within the FIIND domain, which is essential for activation.

  4. Regulatory mechanisms: The model includes negative regulation by DPP8/DPP9, which is an important aspect of inflammasome control.

  5. Cellular localization: The model correctly annotates activities with their subcellular locations.

4. Suggested Improvements

  1. Additional PMID citations: While the model has good literature support, some additional recent papers on NLRP1 activation mechanisms could strengthen the evidence further, particularly for the direct regulatory relationship between NLRP1 molecular condensate scaffold activity and signaling adaptor activity.

  2. Expanded context: The model could benefit from including additional contextual information about what triggers NLRP1 activation in the first place (viral infection, etc.) and the physiological consequences of NLRP1-driven pyroptosis.

  3. Additional components: The model could include IL-1β processing, which is another key outcome of inflammasome activation alongside pyroptosis.

  4. Biological process annotation: While most activities are correctly annotated with 'part_of' biological processes, a more specific annotation for some activities would strengthen the model.

5. Final Assessment

This GO-CAM model accurately represents the NLRP1 inflammasome pathway leading to pyroptosis based on current scientific understanding. It successfully captures the essential molecular activities, their causal relationships, and cellular locations. The model is well-supported by literature evidence and follows GO-CAM curation standards.

The model effectively demonstrates: - The requirement for NLRP1 autolytic processing - Regulation by DPP8/DPP9 - ASC recruitment and inflammasome assembly - Caspase-1 activation - Gasdermin D cleavage and pore formation - Pyroptotic cell death as the final outcome

Overall, this is a high-quality model that provides a valuable resource for understanding NLRP1 inflammasome biology and could serve as a reference for researchers studying inflammasome activation, pyroptosis, and related innate immune processes.