Nutrient chapter

Human ZDHHC7 knockout in HEK293T

11 recorded mechanisms · 2 availability situations · 1 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

  1. Treatment with ML349 did not produce a reported increase in endogenous MAVS S-acylation in HEK293T.

    ML349, experimental APT2 inhibitor → Endogenous MAVS S-acylation in human cells source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls
    exposure
    Inhibitor treatment; dose and duration unresolved; no RLR stimulation specified in S2C.
    limitations
    Null under the reported assay, not proof of no effect at other sites, durations or activation states. Figure S2C and its legend visually reviewed. Exact inhibitor concentrations/durations were not located in the main methods or S2 legend; no matched exposure comparison with the Molecular Cell 2024 study is established.
    organism
    Human
    primary_locator
    SI Appendix Figure S2C; main Results: MAVS Is S-Palmitoylated by ZDHHC7.
    primary_references
    https://doi.org/10.1073/pnas.2403392121

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 6–12

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls · source_derived_draft · unverified_draft

    Treatment with ML349 did not produce a reported increase in endogenous MAVS S-acylation in HEK293T. primary_references: https://doi.org/10.1073/pnas.2403392121 primary_locator: SI Appendix Figure S2C; main Results: MAVS Is S-Palmitoylated by ZDHHC7. organism: Human experimental_model: Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls exposure: Inhibitor treatment; dose and duration unresolved; no RLR stimulation specified in S2C. limitations: Null under the reported assay, not proof of no effect at other sites, durations or activation states. Figure S2C and its legend visually reviewed. Exact inhibitor concentrations/durations were not located in the main methods or S2 legend; no matched exposure comparison with the Molecular Cell 2024 study is established.
    Complete structured claim and evidence

  2. Treatment with ML348 did not produce a reported increase in endogenous MAVS S-acylation in HEK293T.

    ML348, experimental APT1 inhibitor → Endogenous MAVS S-acylation in human cells source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls
    exposure
    Inhibitor treatment; dose and duration unresolved; no RLR stimulation specified in S2C.
    limitations
    Null under the reported assay, not proof of no effect at other sites, durations or activation states. Figure S2C and its legend visually reviewed. Exact inhibitor concentrations/durations were not located in the main methods or S2 legend; no matched exposure comparison with the Molecular Cell 2024 study is established.
    organism
    Human
    primary_locator
    SI Appendix Figure S2C; main Results: MAVS Is S-Palmitoylated by ZDHHC7.
    primary_references
    https://doi.org/10.1073/pnas.2403392121

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 15–21

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls · source_derived_draft · unverified_draft

    Treatment with ML348 did not produce a reported increase in endogenous MAVS S-acylation in HEK293T. primary_references: https://doi.org/10.1073/pnas.2403392121 primary_locator: SI Appendix Figure S2C; main Results: MAVS Is S-Palmitoylated by ZDHHC7. organism: Human experimental_model: Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls exposure: Inhibitor treatment; dose and duration unresolved; no RLR stimulation specified in S2C. limitations: Null under the reported assay, not proof of no effect at other sites, durations or activation states. Figure S2C and its legend visually reviewed. Exact inhibitor concentrations/durations were not located in the main methods or S2 legend; no matched exposure comparison with the Molecular Cell 2024 study is established.
    Complete structured claim and evidence

  3. Treatment with PALMOSTATIN-B did not produce a reported increase in endogenous MAVS S-acylation in HEK293T.

    Palmostatin B, experimental depalmitoylase inhibitor → Endogenous MAVS S-acylation in human cells source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls
    exposure
    Inhibitor treatment; dose and duration unresolved; no RLR stimulation specified in S2C.
    limitations
    Null under the reported assay, not proof of no effect at other sites, durations or activation states. Figure S2C and its legend visually reviewed. Exact inhibitor concentrations/durations were not located in the main methods or S2 legend; no matched exposure comparison with the Molecular Cell 2024 study is established.
    organism
    Human
    primary_locator
    SI Appendix Figure S2C; main Results: MAVS Is S-Palmitoylated by ZDHHC7.
    primary_references
    https://doi.org/10.1073/pnas.2403392121

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 24–30

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls · source_derived_draft · unverified_draft

    Treatment with PALMOSTATIN-B did not produce a reported increase in endogenous MAVS S-acylation in HEK293T. primary_references: https://doi.org/10.1073/pnas.2403392121 primary_locator: SI Appendix Figure S2C; main Results: MAVS Is S-Palmitoylated by ZDHHC7. organism: Human experimental_model: Human HEK293T; endogenous MAVS; acyl-biotin exchange with hydroxylamine-minus controls exposure: Inhibitor treatment; dose and duration unresolved; no RLR stimulation specified in S2C. limitations: Null under the reported assay, not proof of no effect at other sites, durations or activation states. Figure S2C and its legend visually reviewed. Exact inhibitor concentrations/durations were not located in the main methods or S2 legend; no matched exposure comparison with the Molecular Cell 2024 study is established.
    Complete structured claim and evidence

  4. ZDHHC7 knockout decreased endogenous MAVS S-acylation in HEK293T.

    Human ZDHHC7 knockout in HEK293T → Endogenous MAVS S-acylation in human cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Human HEK293T; endogenous proteins; acyl-biotin exchange
    exposure
    Genetic ZDHHC7 knockout.
    limitations
    Endogenous knockout is distinct from murine ZDHHC plasmid overexpression elsewhere in this paper. ABE measures S-acylation, not the abundance of a specified acyl chain.
    organism
    Human
    primary_locator
    Figure 1C; SI Figure S1E, n=5.
    primary_references
    https://doi.org/10.1073/pnas.2403392121
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 33–39

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Human HEK293T; endogenous proteins; acyl-biotin exchange · source_derived_draft · unverified_draft

    ZDHHC7 knockout decreased endogenous MAVS S-acylation in HEK293T. primary_references: https://doi.org/10.1073/pnas.2403392121 primary_locator: Figure 1C; SI Figure S1E, n=5. organism: Human experimental_model: Human HEK293T; endogenous proteins; acyl-biotin exchange exposure: Genetic ZDHHC7 knockout. limitations: Endogenous knockout is distinct from murine ZDHHC plasmid overexpression elsewhere in this paper. ABE measures S-acylation, not the abundance of a specified acyl chain.
    Complete structured claim and evidence

  5. ZDHHC7 knockout reduced MAVS aggregation after poly(I:C) stimulation in HEK293T.

    Human ZDHHC7 knockout in HEK293T → MAVS aggregation in human cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Human HEK293T; wild-type versus ZDHHC7 knockout
    exposure
    Poly(I:C) transfection, 2 micrograms/mL for 8 hours.
    limitations
    Activation-dependent result. Crude P5 includes other organelles; this observation alone does not quantify purified mitochondrial localization.
    organism
    Human
    primary_locator
    Figure 1K; SDD-AGE of crude mitochondrial P5.
    primary_references
    https://doi.org/10.1073/pnas.2403392121
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 42–48

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Human HEK293T; wild-type versus ZDHHC7 knockout · source_derived_draft · unverified_draft

    ZDHHC7 knockout reduced MAVS aggregation after poly(I:C) stimulation in HEK293T. primary_references: https://doi.org/10.1073/pnas.2403392121 primary_locator: Figure 1K; SDD-AGE of crude mitochondrial P5. organism: Human experimental_model: Human HEK293T; wild-type versus ZDHHC7 knockout exposure: Poly(I:C) transfection, 2 micrograms/mL for 8 hours. limitations: Activation-dependent result. Crude P5 includes other organelles; this observation alone does not quantify purified mitochondrial localization.
    Complete structured claim and evidence

  6. ML349 increased the reported IRF3 phosphorylation response despite MAVS knockout in stimulated RAW 264.7 cells.

    ML349, experimental APT2 inhibitor → IRF3 phosphorylation in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Mouse RAW 264.7; Mavs knockout
    exposure
    ML349 10 micromolar for 12 hours, then freeze-thawed Plasmodium yoelii N67 infected red blood cells for 6 hours.
    limitations
    MAVS loss reduces the baseline response. TBK1 loss removes a central signaling node; failure of rescue supports dependence but does not alone prove direct ML349 binding to TBK1. Not a viral infection experiment.
    organism
    Mouse
    primary_locator
    Figure 4j and corresponding Results; IFN-I activation is assessed here by immunoblot, not secreted interferon measurement.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 51–57

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse RAW 264.7; Mavs knockout · source_derived_draft · unverified_draft

    ML349 increased the reported IRF3 phosphorylation response despite MAVS knockout in stimulated RAW 264.7 cells. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 4j and corresponding Results; IFN-I activation is assessed here by immunoblot, not secreted interferon measurement. organism: Mouse experimental_model: Mouse RAW 264.7; Mavs knockout exposure: ML349 10 micromolar for 12 hours, then freeze-thawed Plasmodium yoelii N67 infected red blood cells for 6 hours. limitations: MAVS loss reduces the baseline response. TBK1 loss removes a central signaling node; failure of rescue supports dependence but does not alone prove direct ML349 binding to TBK1. Not a viral infection experiment.
    Complete structured claim and evidence

  7. ML349 failed to restore the reported IRF3 phosphorylation response in TBK1-knockout RAW 264.7 cells.

    ML349, experimental APT2 inhibitor → IRF3 phosphorylation in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Mouse RAW 264.7; Tbk1 knockout
    exposure
    ML349 10 micromolar for 12 hours, then freeze-thawed Plasmodium yoelii N67 infected red blood cells for 6 hours.
    limitations
    MAVS loss reduces the baseline response. TBK1 loss removes a central signaling node; failure of rescue supports dependence but does not alone prove direct ML349 binding to TBK1. Not a viral infection experiment.
    organism
    Mouse
    primary_locator
    Figure 4j and corresponding Results; IFN-I activation is assessed here by immunoblot, not secreted interferon measurement.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 60–66

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse RAW 264.7; Tbk1 knockout · source_derived_draft · unverified_draft

    ML349 failed to restore the reported IRF3 phosphorylation response in TBK1-knockout RAW 264.7 cells. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 4j and corresponding Results; IFN-I activation is assessed here by immunoblot, not secreted interferon measurement. organism: Mouse experimental_model: Mouse RAW 264.7; Tbk1 knockout exposure: ML349 10 micromolar for 12 hours, then freeze-thawed Plasmodium yoelii N67 infected red blood cells for 6 hours. limitations: MAVS loss reduces the baseline response. TBK1 loss removes a central signaling node; failure of rescue supports dependence but does not alone prove direct ML349 binding to TBK1. Not a viral infection experiment.
    Complete structured claim and evidence

  8. ML349 increased TBK1 palmitoylation in mouse peritoneal macrophages.

    ML349, experimental APT2 inhibitor → TBK1 palmitoylation in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Mouse peritoneal exudate macrophages
    exposure
    ML349 concentration series for 12 hours; individual concentrations not transcribed from figure.
    limitations
    Concentration-response result; ABE is an S-acylation assay. No GPX4 endpoint in this experiment.
    organism
    Mouse
    primary_locator
    Figure 3b; ABE and immunoblot.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 69–75

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse peritoneal exudate macrophages · source_derived_draft · unverified_draft

    ML349 increased TBK1 palmitoylation in mouse peritoneal macrophages. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 3b; ABE and immunoblot. organism: Mouse experimental_model: Mouse peritoneal exudate macrophages exposure: ML349 concentration series for 12 hours; individual concentrations not transcribed from figure. limitations: Concentration-response result; ABE is an S-acylation assay. No GPX4 endpoint in this experiment.
    Complete structured claim and evidence

  9. LYPLA2 knockout prevented the reported stimulus-associated decline in TBK1 palmitoylation.

    Mouse LYPLA2 knockout in RAW 264.7 → TBK1 palmitoylation in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Mouse RAW 264.7; wild-type versus Lypla2 knockout
    exposure
    Plasmodium gDNA stimulation for 12 hours; concentration unresolved in this extraction.
    limitations
    Positive denotes preservation relative to stimulated wild-type, not an unqualified increase above resting baseline. No GPX4 endpoint.
    organism
    Mouse
    primary_locator
    Figure 3c; ABE and immunoblot.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 78–84

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse RAW 264.7; wild-type versus Lypla2 knockout · source_derived_draft · unverified_draft

    LYPLA2 knockout prevented the reported stimulus-associated decline in TBK1 palmitoylation. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 3c; ABE and immunoblot. organism: Mouse experimental_model: Mouse RAW 264.7; wild-type versus Lypla2 knockout exposure: Plasmodium gDNA stimulation for 12 hours; concentration unresolved in this extraction. limitations: Positive denotes preservation relative to stimulated wild-type, not an unqualified increase above resting baseline. No GPX4 endpoint.
    Complete structured claim and evidence

  10. Recombinant mouse IFN-beta increased APT2 protein expression in peritoneal macrophages.

    Mouse interferon beta / IFNB1 → APT2 protein abundance in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Mouse peritoneal exudate macrophages
    exposure
    Recombinant IFN-beta at 0, 3, 6 and 12 hours (Figure 7c visually reviewed); exact dose unresolved.
    limitations
    No measurement of APT2 membrane localization, catalytic flux or GPX4 turnover. Protein induction does not establish increased activity toward every APT2 substrate.
    organism
    Mouse
    primary_locator
    Figure 7c; immunoblot and corresponding Results.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 87–93

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse peritoneal exudate macrophages · source_derived_draft · unverified_draft

    Recombinant mouse IFN-beta increased APT2 protein expression in peritoneal macrophages. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 7c; immunoblot and corresponding Results. organism: Mouse experimental_model: Mouse peritoneal exudate macrophages exposure: Recombinant IFN-beta at 0, 3, 6 and 12 hours (Figure 7c visually reviewed); exact dose unresolved. limitations: No measurement of APT2 membrane localization, catalytic flux or GPX4 turnover. Protein induction does not establish increased activity toward every APT2 substrate.
    Complete structured claim and evidence

  11. IFNAR deficiency reduced infected-red-cell-induced APT2 transcript expression in peritoneal macrophages.

    Mouse IFNAR-deficient peritoneal macrophages → APT2 transcript abundance in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    experimental_model
    Mouse wild-type versus Ifnar-deficient peritoneal exudate macrophages
    exposure
    Freeze-thawed Plasmodium yoelii N67 infected red blood cells at 0, 6, 12 and 24 hours (Figure 7d visually reviewed).
    limitations
    The manuscript calls the genotype Ifnar-deficient; this extraction does not assign a specific disrupted subunit allele. No specific IFNAR1 or IFNAR2 state link is inferred.
    organism
    Mouse
    primary_locator
    Figure 7d; RT-qPCR and Results.
    primary_references
    https://doi.org/10.1038/s41467-025-65081-8
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    MAVS inhibitor nulls and APT2-TBK1 immune feedback · lines 96–102

    Selected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · supports · Mouse wild-type versus Ifnar-deficient peritoneal exudate macrophages · source_derived_draft · unverified_draft

    IFNAR deficiency reduced infected-red-cell-induced APT2 transcript expression in peritoneal macrophages. primary_references: https://doi.org/10.1038/s41467-025-65081-8 primary_locator: Figure 7d; RT-qPCR and Results. organism: Mouse experimental_model: Mouse wild-type versus Ifnar-deficient peritoneal exudate macrophages exposure: Freeze-thawed Plasmodium yoelii N67 infected red blood cells at 0, 6, 12 and 24 hours (Figure 7d visually reviewed). limitations: The manuscript calls the genotype Ifnar-deficient; this extraction does not assign a specific disrupted subunit allele. No specific IFNAR1 or IFNAR2 state link is inferred.
    Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

ZDHHC7 knockout decreased endogenous MAVS S-acylation in HEK293T.

Condition: machinery_impairment · Genetic ZDHHC7 knockout.

Normal role: The named molecular machinery participates in the measured immune-signaling experiment; this is not a dietary nutrient shortage.

Recorded consequence: ZDHHC7 knockout decreased endogenous MAVS S-acylation in HEK293T.

Scope: Human HEK293T; endogenous proteins; acyl-biotin exchange

ZDHHC7 knockout reduced MAVS aggregation after poly(I:C) stimulation in HEK293T.

Condition: machinery_impairment · Poly(I:C) transfection, 2 micrograms/mL for 8 hours.

Normal role: The named molecular machinery participates in the measured immune-signaling experiment; this is not a dietary nutrient shortage.

Recorded consequence: ZDHHC7 knockout reduced MAVS aggregation after poly(I:C) stimulation in HEK293T.

Scope: Human HEK293T; wild-type versus ZDHHC7 knockout

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

  • MAVS inhibitor nulls and APT2-TBK1 immune feedbackSelected primary observations: 10.1073/pnas.2403392121; 10.1038/s41467-025-65081-8. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

    Open questions in this collection

    Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

      Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

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