Human activating transcription factor 4 / ATF4

evidence_span

{"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"}

experimental_model

Human promoter reporters, binding assays and overexpression

exposure

ER stress, ATF4 and CHAC1 expression

limitations

Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Human

plain_language

A stress-response factor can turn on glutathione breakdown.

primary_references

[glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144

tissue_or_cell_type

HEK293 and U2OS cells

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 567–578

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human promoter reporters, binding assays and overexpression · source_derived_draft · unverified_draft

### glutathione-atf4-chac1 ATF4-responsive promoter elements supported human CHAC1 transcription in reporter experiments. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stress-response factor can turn on glutathione breakdown. organism: Human tissue_or_cell_type: HEK293 and U2OS cells experimental_model: Human promoter reporters, binding assays and overexpression limitations: Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis. exposure: ER stress, ATF4 and CHAC1 expression evidence_span: {"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"} [glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144

evidence_span

{"source_cache": "artifacts/glutathione-research/40736010.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e", "start_char": 0, "end_char": 1513, "text_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e"}

experimental_model

Genetic screens, cancer models and patient-derived xenografts

exposure

SLC25A39 loss and ATF4 CRISPR activation

limitations

Cancer-specific mechanism; no inference that dietary or supplemental GSH causes metastasis in people.

nutrient_topic

Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH

organism

Experimental breast-cancer cells and mouse xenografts

plain_language

A stress-response pathway provided a bypass in these models.

primary_references

[glutathione-p40736010] Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling. (2025). https://pubmed.ncbi.nlm.nih.gov/40736010/ DOI: 10.1158/2159-8290.cd-24-1556

tissue_or_cell_type

Early lung metastatic colonization

Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1347–1358

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic screens, cancer models and patient-derived xenografts · source_derived_draft · unverified_draft

### glutathione-atf4-metastasis-rescue ATF4 activation restored metastatic potential in A39-deficient experimental cells. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stress-response pathway provided a bypass in these models. organism: Experimental breast-cancer cells and mouse xenografts tissue_or_cell_type: Early lung metastatic colonization experimental_model: Genetic screens, cancer models and patient-derived xenografts limitations: Cancer-specific mechanism; no inference that dietary or supplemental GSH causes metastasis in people. exposure: SLC25A39 loss and ATF4 CRISPR activation evidence_span: {"source_cache": "artifacts/glutathione-research/40736010.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e", "start_char": 0, "end_char": 1513, "text_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e"} [glutathione-p40736010] Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling. (2025). https://pubmed.ncbi.nlm.nih.gov/40736010/ DOI: 10.1158/2159-8290.cd-24-1556

access_level

selected_indexed_full_text_passages

dose

Unresolved; not inferred from another panel

duration

72-hour siRNA; CCCP during final 16 hours

endpoint

ATF4/ISR immunoblot readout

evidence_cache

artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21

experimental_model

HeLa

exposure

CCCP concentration unresolved

limitations

Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.

organism

Human

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6I/J

primary_references

https://doi.org/10.1016/j.molcel.2023.05.031

Requirements for iron-triggered DELE1 signaling · lines 34–45

Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · supports · HeLa · source_derived_draft · unverified_draft

ABCB7 knockdown did not similarly impair the tested CCCP-induced ISR. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6I/J evidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21 access_level: selected_indexed_full_text_passages organism: Human experimental_model: HeLa duration: 72-hour siRNA; CCCP during final 16 hours exposure: CCCP concentration unresolved dose: Unresolved; not inferred from another panel endpoint: ATF4/ISR immunoblot readout limitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.

access_level

selected_indexed_full_text_passages

dose

Unresolved; not inferred from another panel

duration

72-hour siRNA; chelator during final 16 hours

endpoint

ATF4/ISR immunoblot readout

evidence_cache

artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21

experimental_model

HeLa

exposure

DFO or DFP; concentrations unresolved

limitations

Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.

organism

Human

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6I/J

primary_references

https://doi.org/10.1016/j.molcel.2023.05.031

Requirements for iron-triggered DELE1 signaling · lines 6–17

Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · supports · HeLa · source_derived_draft · unverified_draft

ABCB7 knockdown attenuated iron-chelator-induced ATF4 expression. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 6I/J evidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21 access_level: selected_indexed_full_text_passages organism: Human experimental_model: HeLa duration: 72-hour siRNA; chelator during final 16 hours exposure: DFO or DFP; concentrations unresolved dose: Unresolved; not inferred from another panel endpoint: ATF4/ISR immunoblot readout limitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.

access_level

selected_indexed_full_text_passages

dose

Unresolved; not inferred from another panel

duration

72-hour siRNA reported; exact supplementary exposure schedule unresolved

endpoint

ATF4/ISR immunoblot readout

evidence_cache

artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21

experimental_model

Human cultured cells; precise supplementary-panel cell assignment unresolved

exposure

Iron chelation; panel-specific agent and concentration unresolved

limitations

Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.

organism

Human

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results discussing Figure S6B/C

primary_references

https://doi.org/10.1016/j.molcel.2023.05.031

Requirements for iron-triggered DELE1 signaling · lines 48–59

Primary study 10.1016/j.molcel.2023.05.031; targeted counterevidence curation, 2026-09-20. · supports · Human cultured cells; precise supplementary-panel cell assignment unresolved · source_derived_draft · unverified_draft

ISCU depletion attenuated iron-chelation-induced ISR activation. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Results discussing Figure S6B/C evidence_cache: artifacts/discovery-research/round2-sources/iscu-counterevidence-search.json; SHA256 91e6dd454b1fdecf0cf4d29d2579bf1eba148109e446059f91ea966f8bf0de21 access_level: selected_indexed_full_text_passages organism: Human experimental_model: Human cultured cells; precise supplementary-panel cell assignment unresolved duration: 72-hour siRNA reported; exact supplementary exposure schedule unresolved exposure: Iron chelation; panel-specific agent and concentration unresolved dose: Unresolved; not inferred from another panel endpoint: ATF4/ISR immunoblot readout limitations: Selected primary Results and figure legends accessed through indexed text. Supplements were not independently inspected. These results constrain a hypothesis; they do not test SLC25A39 loss or establish its bypass. Exact iron sensor and transporter substrate remain unresolved.

access_level

selected_indexed_full_text_passages

evidence_cache

artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3

experimental_model

MDA-MB-231

exposure

1% oxygen; 12/24 hours

limitations

Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.

organism

Human cultured cells; mouse xenograft host only for colonization endpoint

plain_language

SLC25A39 knockout attenuated hypoxic ATF4 induction in MDA-MB-231 cells.

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4E

primary_references

https://doi.org/10.1158/2159-8290.CD-24-1556

DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 31–40

Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · MDA-MB-231 · source_derived_draft · unverified_draft

SLC25A39 knockout attenuated hypoxic ATF4 induction in MDA-MB-231 cells. primary_references: https://doi.org/10.1158/2159-8290.CD-24-1556 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4E evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: MDA-MB-231 organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: 1% oxygen; 12/24 hours limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: SLC25A39 knockout attenuated hypoxic ATF4 induction in MDA-MB-231 cells.

access_level

selected_indexed_full_text_passages

evidence_cache

artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3

experimental_model

HEK293-derived knockout clones 24/51

exposure

16 hours; DFP 1 mM in its arm; DFO concentration unresolved

limitations

Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.

organism

Human cultured cells; mouse xenograft host only for colonization endpoint

plain_language

DELE1 knockout suppressed iron-chelation-induced ATF4 activation.

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4H

primary_references

https://doi.org/10.1016/j.molcel.2023.05.031

DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 103–112

Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · HEK293-derived knockout clones 24/51 · source_derived_draft · unverified_draft

DELE1 knockout suppressed iron-chelation-induced ATF4 activation. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4H evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: HEK293-derived knockout clones 24/51 organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: 16 hours; DFP 1 mM in its arm; DFO concentration unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: DELE1 knockout suppressed iron-chelation-induced ATF4 activation.

access_level

selected_indexed_full_text_passages

evidence_cache

artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3

experimental_model

MDA-MB-231; HCC1806-LM2

exposure

Overexpression; amount and duration unresolved

limitations

Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.

organism

Human cultured cells; mouse xenograft host only for colonization endpoint

plain_language

DELE1 overexpression increased ATF4 in MDA-MB-231 and HCC1806-LM2 cells.

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4C

primary_references

https://doi.org/10.1158/2159-8290.CD-24-1556

DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 7–16

Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · MDA-MB-231; HCC1806-LM2 · source_derived_draft · unverified_draft

DELE1 overexpression increased ATF4 in MDA-MB-231 and HCC1806-LM2 cells. primary_references: https://doi.org/10.1158/2159-8290.CD-24-1556 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4C evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: MDA-MB-231; HCC1806-LM2 organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: Overexpression; amount and duration unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: DELE1 overexpression increased ATF4 in MDA-MB-231 and HCC1806-LM2 cells.

access_level

selected_indexed_full_text_passages

evidence_cache

artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3

experimental_model

HeLa

exposure

DFO/DFP; final 16 hours after 72-hour siRNA experiment

limitations

Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.

organism

Human cultured cells; mouse xenograft host only for colonization endpoint

plain_language

HRI knockdown suppressed iron-chelator-induced ISR activation.

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4G; S3C/D

primary_references

https://doi.org/10.1016/j.molcel.2023.05.031

DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 79–88

Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · HeLa · source_derived_draft · unverified_draft

HRI knockdown suppressed iron-chelator-induced ISR activation. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 4G; S3C/D evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: HeLa organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: DFO/DFP; final 16 hours after 72-hour siRNA experiment limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: HRI knockdown suppressed iron-chelator-induced ISR activation.

access_level

selected_indexed_full_text_passages

evidence_cache

artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3

experimental_model

HEK293T; HeLa

exposure

DFO/DFP; exact panel dose/time unresolved

limitations

Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.

organism

Human cultured cells; mouse xenograft host only for colonization endpoint

plain_language

OMA1 knockdown did not suppress the tested iron-chelation-induced ISR.

primary_locator

https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 5C/D

primary_references

https://doi.org/10.1016/j.molcel.2023.05.031

DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 91–100

Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · HEK293T; HeLa · source_derived_draft · unverified_draft

OMA1 knockdown did not suppress the tested iron-chelation-induced ISR. primary_references: https://doi.org/10.1016/j.molcel.2023.05.031 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC10329284/ Figure 5C/D evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: HEK293T; HeLa organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: DFO/DFP; exact panel dose/time unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: OMA1 knockdown did not suppress the tested iron-chelation-induced ISR.

evidence_span

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experimental_model

Time-course immunoblotting and ER-stress gene expression

exposure

10 µM boric acid; early time points from 30 minutes

limitations

Expression changes do not establish direct molecular targets or clinical effects. Total eIF2α abundance is distinct from Ser51 phosphorylation. The study did not activate every ER-stress branch.

nutrient_topic

Boron research collection; topical membership is not evidence of a direct dietary effect. · Boron

organism

Human DU-145 cells

plain_language

A regulator of the cellular stress response increased.

primary_references

[boron-p27587023] Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake. (2017). https://pubmed.ncbi.nlm.nih.gov/27587023/ DOI: 10.1007/s12011-016-0824-y

tissue_or_cell_type

Prostate cancer cell culture

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 391–402

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Time-course immunoblotting and ER-stress gene expression · source_derived_draft · unverified_draft

### boron-atf4-abundance Boric acid increased ATF4 protein at one hour in DU-145 cells. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A regulator of the cellular stress response increased. organism: Human DU-145 cells tissue_or_cell_type: Prostate cancer cell culture experimental_model: Time-course immunoblotting and ER-stress gene expression limitations: Expression changes do not establish direct molecular targets or clinical effects. Total eIF2α abundance is distinct from Ser51 phosphorylation. The study did not activate every ER-stress branch. exposure: 10 µM boric acid; early time points from 30 minutes evidence_span: {"source_cache": "artifacts/boron-research/27587023.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "421c3ea56e2b1058bb780928a63bb648246560a0ba3a070d82dc3fdd37ff0725", "start_char": 0, "end_char": 1886, "text_sha256": "421c3ea56e2b1058bb780928a63bb648246560a0ba3a070d82dc3fdd37ff0725"} [boron-p27587023] Activation of the EIF2α/ATF4 and ATF6 Pathways in DU-145 Cells by Boric Acid at the Concentration Reported in Men at the US Mean Boron Intake. (2017). https://pubmed.ncbi.nlm.nih.gov/27587023/ DOI: 10.1007/s12011-016-0824-y

evidence_span

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experimental_model

Human prostate cancer cell stress-response assays

exposure

Boric-acid exposure in the physiological-range conditions reported by the study

limitations

This study measured stress responses in a tumor cell line. Proposed consequences for bone differentiation or cancer risk were not tested clinical outcomes.

nutrient_topic

Boron research collection; topical membership is not evidence of a direct dietary effect. · Boron

organism

Human DU-145 cells

plain_language

These cells reorganized parts of their protein-making machinery as a mild stress response.

primary_references

[boron-p25425213] Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25425213/ DOI: 10.1007/s10534-014-9809-5

tissue_or_cell_type

Prostate cancer cell culture

Boron: chemistry, nutrient interactions, low-intake studies and mechanistic uncertainties (2026-09-17) · lines 365–376

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human prostate cancer cell stress-response assays · source_derived_draft · unverified_draft

### boron-stress-granules Boric-acid treatment induced stress granules and mild activation of the eIF2α/ATF4 response in DU-145 cells. Condition category: normal nutrient_topic: Boron research collection; topical membership is not evidence of a direct dietary effect. plain_language: These cells reorganized parts of their protein-making machinery as a mild stress response. organism: Human DU-145 cells tissue_or_cell_type: Prostate cancer cell culture experimental_model: Human prostate cancer cell stress-response assays limitations: This study measured stress responses in a tumor cell line. Proposed consequences for bone differentiation or cancer risk were not tested clinical outcomes. exposure: Boric-acid exposure in the physiological-range conditions reported by the study evidence_span: {"source_cache": "artifacts/boron-research/25425213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5bd1560c24d673e3b1d1fc3d44f0c910ac981ffd2f53a3b90c6259f136c69fca", "start_char": 0, "end_char": 1068, "text_sha256": "5bd1560c24d673e3b1d1fc3d44f0c910ac981ffd2f53a3b90c6259f136c69fca"} [boron-p25425213] Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25425213/ DOI: 10.1007/s10534-014-9809-5