Component
Insulin-induced gene 2 protein (INSIG2)
Human INSIG2 endoplasmic-reticulum regulatory protein.
2 recorded relationships. Experimental role, claim status and evidence remain attached to each record.
How nutrients influence it
Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.
Other things that act on it
Enzymes, hormones, genes, and other components with a recorded effect. These are not nutrients, so they do not count toward the arrows above. Each finding names the chapter that recorded it.
How nutrients reach it in more than one step
Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.
Tracing routes…
What it does
Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.
Where it participates (unsigned role)
Delta-tocotrienol stimulated HMG-CoA reductase ubiquitination in isolated SV-589 fibroblast membrane fractions supplemented with ubiquitin-activating enzyme; gamma-tocotrienol showed the same activity. The reconstituted result supported action without further tocotrienol metabolism.
Experimental context and source evidence
- cross_nutrient
- false
- experimental_model
- Isolated membranes from sterol-depleted SV-589 human fibroblasts; FLAG-ubiquitin and purified E1 assay
- exposure
- Figure 5B: purified E1 5 µg/mL, FLAG-ubiquitin 0.1 mg/mL, ubiquitin-aldehyde 0.01 mg/mL and ATP-regenerating system; tocotrienol concentration not fully retrieved.
- limitations
- The assay does not prove direct molecular binding of tocotrienol to HMGCR or INSIG. No human cholesterol outcome follows from this reconstituted experiment.
- nutrient_topic
- Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
- organism
- Homo sapiens
- plain_language
- These tocotrienols promoted attachment of degradation tags to the cholesterol-synthesis enzyme in isolated cell membranes.
- primary_references
- [song2006] Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. (2006). https://pubmed.ncbi.nlm.nih.gov/16831864/ DOI: 10.1074/jbc.m605575200
- tissue_or_cell_type
- Fibroblast-derived membrane fractions
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1128–1139
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated membranes from sterol-depleted SV-589 human fibroblasts; FLAG-ubiquitin and purified E1 assay · source_derived_draft · unverified_draft
### e-sig-delta-te-hmgcr-ubiquitination Delta-tocotrienol stimulated HMG-CoA reductase ubiquitination in isolated SV-589 fibroblast membrane fractions supplemented with ubiquitin-activating enzyme; gamma-tocotrienol showed the same activity. The reconstituted result supported action without further tocotrienol metabolism. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: These tocotrienols promoted attachment of degradation tags to the cholesterol-synthesis enzyme in isolated cell membranes. organism: Homo sapiens tissue_or_cell_type: Fibroblast-derived membrane fractions experimental_model: Isolated membranes from sterol-depleted SV-589 human fibroblasts; FLAG-ubiquitin and purified E1 assay limitations: The assay does not prove direct molecular binding of tocotrienol to HMGCR or INSIG. No human cholesterol outcome follows from this reconstituted experiment. exposure: Figure 5B: purified E1 5 µg/mL, FLAG-ubiquitin 0.1 mg/mL, ubiquitin-aldehyde 0.01 mg/mL and ATP-regenerating system; tocotrienol concentration not fully retrieved. cross_nutrient: false [song2006] Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. (2006). https://pubmed.ncbi.nlm.nih.gov/16831864/ DOI: 10.1074/jbc.m605575200
Complete structured claim and evidenceCombined RNAi against INSIG1 and INSIG2 abolished gamma- and delta-tocotrienol-stimulated degradation of endogenous HMG-CoA reductase in sterol-depleted SV-589 fibroblasts supplied with 10 mM mevalonate.
Experimental context and source evidence
- availability_state
- machinery_impairment Imported condition classification; unverified.
- cross_nutrient
- false
- experimental_model
- Combined INSIG1/INSIG2 RNA interference in immortalized human SV-589 fibroblasts
- exposure
- Sterol depletion 16 h; gamma- or delta-tocotrienol plus 10 mM mevalonate for 5 h; tocotrienol concentration not retrieved from the accessible Figure 3 text.
- limitations
- Combined knockdown establishes a machinery requirement in this model, not the unique role of either INSIG isoform or nutritional deficiency. Does not quantify viability or predict supplement benefit.
- nutrient_topic
- Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
- organism
- Homo sapiens
- plain_language
- Removing both INSIG regulators prevented these tocotrienols from accelerating loss of the reductase protein in this cell experiment.
- primary_references
- [song2006] Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. (2006). https://pubmed.ncbi.nlm.nih.gov/16831864/ DOI: 10.1074/jbc.m605575200
- tissue_or_cell_type
- Human fibroblast cell culture
- trigger_kind
- machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 1141–1152
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Combined INSIG1/INSIG2 RNA interference in immortalized human SV-589 fibroblasts · source_derived_draft · unverified_draft
### e-sig-insig-depletion-hmgcr-turnover Combined RNAi against INSIG1 and INSIG2 abolished gamma- and delta-tocotrienol-stimulated degradation of endogenous HMG-CoA reductase in sterol-depleted SV-589 fibroblasts supplied with 10 mM mevalonate. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing both INSIG regulators prevented these tocotrienols from accelerating loss of the reductase protein in this cell experiment. organism: Homo sapiens tissue_or_cell_type: Human fibroblast cell culture experimental_model: Combined INSIG1/INSIG2 RNA interference in immortalized human SV-589 fibroblasts limitations: Combined knockdown establishes a machinery requirement in this model, not the unique role of either INSIG isoform or nutritional deficiency. Does not quantify viability or predict supplement benefit. exposure: Sterol depletion 16 h; gamma- or delta-tocotrienol plus 10 mM mevalonate for 5 h; tocotrienol concentration not retrieved from the accessible Figure 3 text. cross_nutrient: false [song2006] Insig-dependent ubiquitination and degradation of 3-hydroxy-3-methylglutaryl coenzyme a reductase stimulated by delta- and gamma-tocotrienols. (2006). https://pubmed.ncbi.nlm.nih.gov/16831864/ DOI: 10.1074/jbc.m605575200
Complete structured claim and evidence
The events it takes part in
A mechanism often involves more than two components. These are the full events, with every participant and its role.
Situations it appears in
Low-supply and faulty-machinery situations recorded in the chapters where this component plays a part.
In the sources
Preserved passages that mention this component, quoted exactly. Open one to read it in context.
Open hypotheses
Proposed ideas that involve this component. They are labeled as hypotheses and do not change any recorded statement.
This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.