Excited to report our discovery of an important component of the oxidative stress response: the E3 ligase TRIP12. It acts as a chain elongation factor that amplifies CUL3-KEAP1 activity to drive NRF2 degradation as cells recover from stress.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12
The oxidative stress response is centered on the transcription factor NRF2 and protects cells from reactive oxygen species (ROS). While ROS inhibit the E3 ligase CUL3-KEAP1 to stabilize NRF2 and elici...
www.biorxiv.org
November 26, 2024 at 2:53 PM
Excited to report our discovery of an important component of the oxidative stress response: the E3 ligase TRIP12. It acts as a chain elongation factor that amplifies CUL3-KEAP1 activity to drive NRF2 degradation as cells recover from stress.
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
🚨Out today in @natureportfolio.bsky.social Nature Communications: Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography🍾
www.nature.com/articles/s41...
In this paper, we show that [18F]FSPG-PET imaging is a sensitive marker of NRF2/KEAP1 activating mutations...
www.nature.com/articles/s41...
In this paper, we show that [18F]FSPG-PET imaging is a sensitive marker of NRF2/KEAP1 activating mutations...
December 17, 2024 at 11:10 AM
🚨Out today in @natureportfolio.bsky.social Nature Communications: Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography🍾
www.nature.com/articles/s41...
In this paper, we show that [18F]FSPG-PET imaging is a sensitive marker of NRF2/KEAP1 activating mutations...
www.nature.com/articles/s41...
In this paper, we show that [18F]FSPG-PET imaging is a sensitive marker of NRF2/KEAP1 activating mutations...
🫀 New therapy helps hearts heal after attack
Scientists have made a protein-like polymer that protects heart cells after a heart attack by calming inflammation and boosting repair.
So far it has been tested successfully in rats.
🔗 doi.org/10.1002/adma...
#SciComm #HeartResearch 🧪
Scientists have made a protein-like polymer that protects heart cells after a heart attack by calming inflammation and boosting repair.
So far it has been tested successfully in rats.
🔗 doi.org/10.1002/adma...
#SciComm #HeartResearch 🧪
Protein‐Like Polymers Targeting Keap1/Nrf2 as Therapeutics for Myocardial Infarction
We describe a Keap1 targeting protein-like polymer (PLP) which activates Nrf2, an important cytoprotective transcription factor for relieving myocardial infarction-induced oxidative stress. This PLP ...
doi.org
April 27, 2025 at 4:47 PM
🫀 New therapy helps hearts heal after attack
Scientists have made a protein-like polymer that protects heart cells after a heart attack by calming inflammation and boosting repair.
So far it has been tested successfully in rats.
🔗 doi.org/10.1002/adma...
#SciComm #HeartResearch 🧪
Scientists have made a protein-like polymer that protects heart cells after a heart attack by calming inflammation and boosting repair.
So far it has been tested successfully in rats.
🔗 doi.org/10.1002/adma...
#SciComm #HeartResearch 🧪
Now in #Science #Immunology: Ziang Zhu, Tuoqi Wu, Chen Yao et al at UT Southwestern show that #NRF2 suppression mediated by the #redox sensor #KEAP1 is required for optimal expansion of #CD8 #TCells during chronic antigen exposure!
The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation
KEAP1 promotes persistent T cell immunity and a stem-like T cell response during chronic antigen stimulation by repressing NRF2.
www.science.org
November 29, 2024 at 7:30 PM
"Using mouse models of acute and chronic viral infection, Zhu et al. found that the KEAP1-mediated suppression of NRF2 was required for optimal expansion of CD8+ T cells during chronic antigen exposure."
#Immunology #Immunotherapy #Immunosky
www.science.org/doi/10.1126/...
#Immunology #Immunotherapy #Immunosky
www.science.org/doi/10.1126/...
The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation
KEAP1 promotes persistent T cell immunity and a stem-like T cell response during chronic antigen stimulation by repressing NRF2.
www.science.org
December 1, 2024 at 9:17 AM
"Using mouse models of acute and chronic viral infection, Zhu et al. found that the KEAP1-mediated suppression of NRF2 was required for optimal expansion of CD8+ T cells during chronic antigen exposure."
#Immunology #Immunotherapy #Immunosky
www.science.org/doi/10.1126/...
#Immunology #Immunotherapy #Immunosky
www.science.org/doi/10.1126/...
KEAP1-mediated suppression of NRF2 required for optimal expansion of CD8+ T cells during chronic antigen exposure:
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation
KEAP1 promotes persistent T cell immunity and a stem-like T cell response during chronic antigen stimulation by repressing NRF2.
www.science.org
November 29, 2024 at 9:32 PM
KEAP1-mediated suppression of NRF2 required for optimal expansion of CD8+ T cells during chronic antigen exposure:
www.science.org/doi/10.1126/...
www.science.org/doi/10.1126/...
KEAP1-NRF2 pathway and expression of antioxidant genes, H/T: @angelifriedmann.bsky.social
December 1, 2024 at 6:09 PM
KEAP1-NRF2 pathway and expression of antioxidant genes, H/T: @angelifriedmann.bsky.social
Our latest, in Science Advances: In vivo CRISPR screen revealed sgRNAs that switch chemosensitive SCLC PDXs to become resistant.We validated KEAP1 as key hit and found KEAP1 alterations in IMpower133 trial, where active NRF2 links to reduced survival in chemo arm www.science.org/doi/10.1126/... 1/2
April 29, 2025 at 10:10 PM
Our latest, in Science Advances: In vivo CRISPR screen revealed sgRNAs that switch chemosensitive SCLC PDXs to become resistant.We validated KEAP1 as key hit and found KEAP1 alterations in IMpower133 trial, where active NRF2 links to reduced survival in chemo arm www.science.org/doi/10.1126/... 1/2
Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction
Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction
Non-covalent targeting of KEAP1 by capsaicin provides a reversible and safe NRF2 agonist for treating oxidative damage.
buff.ly
July 17, 2026 at 8:03 PM
Capsaicin acts as a novel NRF2 agonist to suppress ethanol induced gastric mucosa oxidative damage by directly disrupting the KEAP1-NRF2 interaction
Japanese researchers observe NRF2 is potent anti-#inflammation target
www.nature.com/articles/s41...
In #mouse model of multiple organ dysfunction syndrome #MODS model, NRF2 activation caused:
— decr. inflammatory cytokines
— incr. blood flow, kidney & liver function
— incr. survival
#science 🧪
www.nature.com/articles/s41...
In #mouse model of multiple organ dysfunction syndrome #MODS model, NRF2 activation caused:
— decr. inflammatory cytokines
— incr. blood flow, kidney & liver function
— incr. survival
#science 🧪
CH7450924, a KEAP1-NRF2 interaction inhibitor, ameliorates LPS-induced multiple organ dysfunction via inflammatory pathway inhibition - Scientific Reports
Scientific Reports - CH7450924, a KEAP1-NRF2 interaction inhibitor, ameliorates LPS-induced multiple organ dysfunction via inflammatory pathway inhibition
www.nature.com
October 17, 2025 at 5:46 PM
Japanese researchers observe NRF2 is potent anti-#inflammation target
www.nature.com/articles/s41...
In #mouse model of multiple organ dysfunction syndrome #MODS model, NRF2 activation caused:
— decr. inflammatory cytokines
— incr. blood flow, kidney & liver function
— incr. survival
#science 🧪
www.nature.com/articles/s41...
In #mouse model of multiple organ dysfunction syndrome #MODS model, NRF2 activation caused:
— decr. inflammatory cytokines
— incr. blood flow, kidney & liver function
— incr. survival
#science 🧪
A new paper from Dr. Edwin Miranda, who investigated the effects of suppressing oxidative stress by inhibiting Keap1. Results were somewhat unexpected, but highlighted the importance of nuanced roles that ROS play in muscle function. More papers to come on this related topic!
Muscle‐specific Keap1 deletion enhances force production but does not prevent inactivity‐induced muscle atrophy in mice
In absence of oxidative stress (i.e., Control, left panel) Keap1 binds and ubiquitinates the antioxidant response element (ARE) transcription factor NRF2. Ubiquitinated NRF2 is degraded and unable to....
faseb.onlinelibrary.wiley.com
March 14, 2025 at 5:03 PM
A new paper from Dr. Edwin Miranda, who investigated the effects of suppressing oxidative stress by inhibiting Keap1. Results were somewhat unexpected, but highlighted the importance of nuanced roles that ROS play in muscle function. More papers to come on this related topic!
#Fumarate update
Gang of 3: How the Krebs cycle-linked metabolites itaconate, succinate, and fumarate regulate macrophages & inflammation
Dual role in Inflammation
Anti-
KEAP1-NRF2
GSDMD
NLRP3
IL-10
Pro-
mtDNA mtRNA➡️IFNβ
#CellMetab 2025
www.sciencedirect.com/science/arti...
Gang of 3: How the Krebs cycle-linked metabolites itaconate, succinate, and fumarate regulate macrophages & inflammation
Dual role in Inflammation
Anti-
KEAP1-NRF2
GSDMD
NLRP3
IL-10
Pro-
mtDNA mtRNA➡️IFNβ
#CellMetab 2025
www.sciencedirect.com/science/arti...
June 21, 2025 at 7:47 PM
#Fumarate update
Gang of 3: How the Krebs cycle-linked metabolites itaconate, succinate, and fumarate regulate macrophages & inflammation
Dual role in Inflammation
Anti-
KEAP1-NRF2
GSDMD
NLRP3
IL-10
Pro-
mtDNA mtRNA➡️IFNβ
#CellMetab 2025
www.sciencedirect.com/science/arti...
Gang of 3: How the Krebs cycle-linked metabolites itaconate, succinate, and fumarate regulate macrophages & inflammation
Dual role in Inflammation
Anti-
KEAP1-NRF2
GSDMD
NLRP3
IL-10
Pro-
mtDNA mtRNA➡️IFNβ
#CellMetab 2025
www.sciencedirect.com/science/arti...
CASM regulates p62/KEAP1/NRF2 antioxidant responses to lysosome damage https://www.biorxiv.org/content/10.64898/2026.07.08.736046v1
July 8, 2026 at 3:31 PM
CASM regulates p62/KEAP1/NRF2 antioxidant responses to lysosome damage https://www.biorxiv.org/content/10.64898/2026.07.08.736046v1
Please check out our new preprint! We find an unexpected role for #CASM in regulating p62 mediated activation of the KEAP1/NRF2 pathway to initiate a cytoprotective antioxidant transcriptional response. More functions for #CASM in responding to lysosome stress. www.biorxiv.org/content/10.6...
1/2
1/2
CASM regulates p62/KEAP1/NRF2 antioxidant responses to lysosome damage
Effective lysosome function is essential for health, and declines with ageing and disease. Upon lysosome damage, cells mount a complex stress response to restore homeostasis. Membrane ATG8ylation play...
www.biorxiv.org
July 10, 2026 at 8:12 AM
Please check out our new preprint! We find an unexpected role for #CASM in regulating p62 mediated activation of the KEAP1/NRF2 pathway to initiate a cytoprotective antioxidant transcriptional response. More functions for #CASM in responding to lysosome stress. www.biorxiv.org/content/10.6...
1/2
1/2
How do horses meet exceedingly high bioenergetic demands & mitigate oxidative damage?☺️👇
KEAP1 mutation (R15➡️X15) & Opal stop codon (UGA) recoding (X15➡️C15) in Equus🐎 confer hyperactive NRF2, ⏫OXPHOS AND ⏬ROS
Can we edit KEAP1 R15C to make Superman?🥸
#Science 2025
www.science.org/doi/10.1126/...
KEAP1 mutation (R15➡️X15) & Opal stop codon (UGA) recoding (X15➡️C15) in Equus🐎 confer hyperactive NRF2, ⏫OXPHOS AND ⏬ROS
Can we edit KEAP1 R15C to make Superman?🥸
#Science 2025
www.science.org/doi/10.1126/...
May 7, 2025 at 11:57 AM
How do horses meet exceedingly high bioenergetic demands & mitigate oxidative damage?☺️👇
KEAP1 mutation (R15➡️X15) & Opal stop codon (UGA) recoding (X15➡️C15) in Equus🐎 confer hyperactive NRF2, ⏫OXPHOS AND ⏬ROS
Can we edit KEAP1 R15C to make Superman?🥸
#Science 2025
www.science.org/doi/10.1126/...
KEAP1 mutation (R15➡️X15) & Opal stop codon (UGA) recoding (X15➡️C15) in Equus🐎 confer hyperactive NRF2, ⏫OXPHOS AND ⏬ROS
Can we edit KEAP1 R15C to make Superman?🥸
#Science 2025
www.science.org/doi/10.1126/...
KEAP1 promotes persistent T cell immunity and a stem-like T cell response during chronic antigen stimulation by repressing NRF2
www.science.org/doi/epdf/10....
@scienceimmuno.bsky.social
www.science.org/doi/epdf/10....
@scienceimmuno.bsky.social
The redox sensor KEAP1 facilitates adaptation of T cells to chronic antigen stimulation by preventing hyperactivation
You have to enable JavaScript in your browser's settings in order to use the eReader.
www.science.org
November 29, 2024 at 8:42 PM
KEAP1 promotes persistent T cell immunity and a stem-like T cell response during chronic antigen stimulation by repressing NRF2
www.science.org/doi/epdf/10....
@scienceimmuno.bsky.social
www.science.org/doi/epdf/10....
@scienceimmuno.bsky.social
Lin Luan, @jeremybaskin.bsky.social and colleagues @weillinstitute.bsky.social identify the Cullin-3 adaptor SHKBP1 as a non-canonical regulator of p62 phase behavior limiting p62 body formation and affecting Keap1/Nrf2 antioxidant signaling. rupress.org/jcb/article/...
#CellSignaling
#CellSignaling
February 6, 2026 at 5:00 PM
Lin Luan, @jeremybaskin.bsky.social and colleagues @weillinstitute.bsky.social identify the Cullin-3 adaptor SHKBP1 as a non-canonical regulator of p62 phase behavior limiting p62 body formation and affecting Keap1/Nrf2 antioxidant signaling. rupress.org/jcb/article/...
#CellSignaling
#CellSignaling
Excited to announce that our paper on the use of splicing junction for detecting abnormal constitutive activation of the KEAP1-NRF2 system, led by @friend1ws.bsky.social at NCCRI, is now published in @natureportfolio.bsky.social npj Systems Biology and Applications! (1/n)
t.ly/OA9fS
t.ly/OA9fS
December 13, 2024 at 4:48 AM
Excited to announce that our paper on the use of splicing junction for detecting abnormal constitutive activation of the KEAP1-NRF2 system, led by @friend1ws.bsky.social at NCCRI, is now published in @natureportfolio.bsky.social npj Systems Biology and Applications! (1/n)
t.ly/OA9fS
t.ly/OA9fS
🚨New paper alert! Led by former undergrad Amanda Sherwood @tophinogenesis.bsky.social (now PhD student at Northwestern), Amanda asked whether the glutathione or thioredoxin systems are necessary for NRF2's tumor-promoting effects in the lung. www.sciencedirect.com/science/arti...
Distinct roles for the thioredoxin and glutathione antioxidant systems in Nrf2-Mediated lung tumor initiation and progression
Redox regulators are emerging as critical mediators of lung tumorigenesis. NRF2 and its negative regulator KEAP1 are commonly mutated in human lung ca…
www.sciencedirect.com
May 8, 2025 at 5:33 PM
🚨New paper alert! Led by former undergrad Amanda Sherwood @tophinogenesis.bsky.social (now PhD student at Northwestern), Amanda asked whether the glutathione or thioredoxin systems are necessary for NRF2's tumor-promoting effects in the lung. www.sciencedirect.com/science/arti...
Free radicals #17: #16 was esoteric. Keap1 is a protein that senses electrophiles (electron lovers). Polyphenols can be oxidized to become electrophiles. When electrophiles bind to Keap1, another protein, Nrf2, increases and binds to DNA promoting antioxidant enzyme production. 🧪
February 1, 2025 at 8:07 PM
Free radicals #17: #16 was esoteric. Keap1 is a protein that senses electrophiles (electron lovers). Polyphenols can be oxidized to become electrophiles. When electrophiles bind to Keap1, another protein, Nrf2, increases and binds to DNA promoting antioxidant enzyme production. 🧪
Loss of the ubiquitin ligase targeting factor KEAP1 induces NRF2-driven reductive stress, revealing KEAP1-dependent therapeutic vulnerabilities of KEAP1-mutant NSCLC, particularly under metabolic stress
@idikic.bsky.social @diefenbacherlab.bsky.social and coworkers
link.springer.com/article/10.1...
@idikic.bsky.social @diefenbacherlab.bsky.social and coworkers
link.springer.com/article/10.1...
Targeting ubiquitin signaling vulnerabilities in KEAP1-inactivated lung cancer - The EMBO Journal
Lung cancer cells rely on protein homeostasis regulators, particularly the ubiquitin-proteasome system (UPS), to sustain malignancy. Genetic alterations in UPS components, such as E3 ubiquitin ligases...
link.springer.com
March 20, 2026 at 12:22 PM
Loss of the ubiquitin ligase targeting factor KEAP1 induces NRF2-driven reductive stress, revealing KEAP1-dependent therapeutic vulnerabilities of KEAP1-mutant NSCLC, particularly under metabolic stress
@idikic.bsky.social @diefenbacherlab.bsky.social and coworkers
link.springer.com/article/10.1...
@idikic.bsky.social @diefenbacherlab.bsky.social and coworkers
link.springer.com/article/10.1...
A potential new immune checkpoint: The KEAP1-NRF2 pathway drives PTGIR expression, inducing CD8+ T cell exhaustion via metabolic changes. Blocking PTGIR enhances T cell function, pointing to alternative immunotherapy targets 💊.
#NRF2 #Immunology #ImmunoSky
🔗 rdcu.be/etTbI
🔗 rdcu.be/etTbb
#NRF2 #Immunology #ImmunoSky
🔗 rdcu.be/etTbI
🔗 rdcu.be/etTbb
June 28, 2025 at 2:17 PM
A potential new immune checkpoint: The KEAP1-NRF2 pathway drives PTGIR expression, inducing CD8+ T cell exhaustion via metabolic changes. Blocking PTGIR enhances T cell function, pointing to alternative immunotherapy targets 💊.
#NRF2 #Immunology #ImmunoSky
🔗 rdcu.be/etTbI
🔗 rdcu.be/etTbb
#NRF2 #Immunology #ImmunoSky
🔗 rdcu.be/etTbI
🔗 rdcu.be/etTbb
Free radicals #16: Polyphenols do not effectively neutralize free radicals or oxidants. When metabolized to an electrophilic form, they can form adducts to Keap1 and thereby induce Nrf2 regulated antioxidant enzymes. 🧪
January 30, 2025 at 5:34 PM
Free radicals #16: Polyphenols do not effectively neutralize free radicals or oxidants. When metabolized to an electrophilic form, they can form adducts to Keap1 and thereby induce Nrf2 regulated antioxidant enzymes. 🧪
Congratulation to Julia FATH, Christel BECKER et al. from @myelinteam-t3s.bsky.social for their new article:
"BDNF exerts an NRF2-dependent cytoprotective function via a receptor-independent pathway"
www.sciencedirect.com/science/arti...
@upcite.bsky.social @inserm.fr
"BDNF exerts an NRF2-dependent cytoprotective function via a receptor-independent pathway"
www.sciencedirect.com/science/arti...
@upcite.bsky.social @inserm.fr
BDNF exerts an NRF2-dependent cytoprotective function via a receptor-independent pathway
The ancestral and ubiquitous KEAP1-NRF2 cellular defense system is controlled by chemical inducers and intracellular proteins. Here, we show that an e…
www.sciencedirect.com
November 26, 2025 at 8:58 AM
Congratulation to Julia FATH, Christel BECKER et al. from @myelinteam-t3s.bsky.social for their new article:
"BDNF exerts an NRF2-dependent cytoprotective function via a receptor-independent pathway"
www.sciencedirect.com/science/arti...
@upcite.bsky.social @inserm.fr
"BDNF exerts an NRF2-dependent cytoprotective function via a receptor-independent pathway"
www.sciencedirect.com/science/arti...
@upcite.bsky.social @inserm.fr