| Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts. | Targeting the EIF2AK1 Signaling Pathway Rescues Red Blood Cell Production in SF3B1-Mutant Myelodysplastic Syndromes With Ringed Sideroblasts.
Adema V, Ma F, Kanagal-Shamanna R, Thongon N, Montalban-Bravo G, Yang H, Peslak SA, Wang F, Acha P, Sole F, Lockyer P, Cassari M, Maciejewski JP, Visconte V, Gañán-Gómez I, Song Y, Bueso-Ramos C, Pellegrini M, Tan TM, Bejar R, Carew JS, Halene S, Santini V, Al-Atrash G, Clise-Dwyer K, Garcia-Manero G, Blobel GA, Colla S., Free PMC Article | 11/5/2022 |
| The eIF2alpha kinase HRI triggers the autophagic clearance of cytosolic protein aggregates. | The eIF2α kinase HRI triggers the autophagic clearance of cytosolic protein aggregates.
Mukherjee T, Ramaglia V, Abdel-Nour M, Bianchi AA, Tsalikis J, Chau HN, Kalia SK, Kalia LV, Chen JJ, Arnoult D, Gommerman JL, Philpott DJ, Girardin SE., Free PMC Article | 08/7/2021 |
| The eIF2alpha kinase HRI in innate immunity, proteostasis, and mitochondrial stress. | The eIF2α kinase HRI in innate immunity, proteostasis, and mitochondrial stress.
Girardin SE, Cuziol C, Philpott DJ, Arnoult D. | 07/24/2021 |
| The HRI-regulated transcription factor ATF4 activates BCL11A transcription to silence fetal hemoglobin expression. | The HRI-regulated transcription factor ATF4 activates BCL11A transcription to silence fetal hemoglobin expression.
Huang P, Peslak SA, Lan X, Khandros E, Yano JA, Sharma M, Keller CA, Giardine B, Qin K, Abdulmalik O, Hardison RC, Shi J, Blobel GA., Free PMC Article | 02/13/2021 |
| mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway; the OMA1-DELE1-HRI pathway represents a potential therapeutic target that could enable fine-tuning of the integrated stress response for beneficial outcomes in diseases that involve mitochondrial dysfunction | Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway.
Guo X, Aviles G, Liu Y, Tian R, Unger BA, Lin YT, Wiita AP, Xu K, Correia MA, Kampmann M., Free PMC Article | 05/30/2020 |
| Human disorders associated with deleterious variants in EIF2AK1 and EIF2AK2 have not been reported. | De novo EIF2AK1 and EIF2AK2 Variants Are Associated with Developmental Delay, Leukoencephalopathy, and Neurologic Decompensation.
Mao D, Reuter CM, Ruzhnikov MRZ, Beck AE, Farrow EG, Emrick LT, Rosenfeld JA, Mackenzie KM, Robak L, Wheeler MT, Burrage LC, Jain M, Liu P, Calame D, Küry S, Sillesen M, Schmitz-Abe K, Tonduti D, Spaccini L, Iascone M, Genetti CA, Koenig MK, Graf M, Tran A, Alejandro M, Undiagnosed Diseases Network, Lee BH, Thiffault I, Agrawal PB, Bernstein JA, Bellen HJ, Chao HT., Free PMC Article | 05/16/2020 |
| Recently, HRI has been implicated in the regulation of human fetal hemoglobin production. Therefore, HRI-integrated stress response has emerged as a potential therapeutic target for hemoglobinopathies. especially under iron/heme deficiency and beta-thalassemia. [review] | Heme-regulated eIF2α kinase in erythropoiesis and hemoglobinopathies.
Chen JJ, Zhang S., Free PMC Article | 03/7/2020 |
| Activation of HRI is mediated by Hsp90 during stress through modulation of the HRI-Hsp90 complex | Activation of HRI is mediated by Hsp90 during stress through modulation of the HRI-Hsp90 complex.
Berwal SK, Bhatia V, Bendre A, Suresh CG, Chatterjee S, Pal JK. | 12/22/2018 |
| Taken together, these results suggest HRI as a potential therapeutic target for hemoglobinopathies. | Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells.
Grevet JD, Lan X, Hamagami N, Edwards CR, Sankaranarayanan L, Ji X, Bhardwaj SK, Face CJ, Posocco DF, Abdulmalik O, Keller CA, Giardine B, Sidoli S, Garcia BA, Chou ST, Liebhaber SA, Hardison RC, Shi J, Blobel GA., Free PMC Article | 09/22/2018 |
| data suggests that glutamatergic stimulation induces HRI activation by NO to trigger GluN2B expression and this process would be relevant to maintain postsynaptic activity in cortical neurons | Glutamatergic stimulation induces GluN2B translation by the nitric oxide-Heme-Regulated eIF2α kinase in cortical neurons.
Ramos-Fernández E, Tajes M, Ill-Raga G, Vargas L, Busquets-García A, Bosch-Morató M, Guivernau B, Valls-Comamala V, Gomis M, Grau C, Fandos C, Rosen MD, Rabinowitz MH, Inestrosa N, Maldonado R, Altafaj X, Ozaita A, Alvarez A, Vicente R, Valverde MA, Muñoz FJ., Free PMC Article | 02/3/2018 |
| The antiviral kinase PKR plays a critical role in controlling HCMV replication. | Mechanism of Protein Kinase R Inhibition by Human Cytomegalovirus pTRS1.
Vincent HA, Ziehr B, Moorman NJ., Free PMC Article | 06/3/2017 |
| structural and functional stability of HRI | HRI, a stress response eIF2α kinase, exhibits structural and functional stability at high temperature and alkaline conditions.
Bhavnani V, Swarnendu K, Savergave L, Raghuwanshi AS, Kumar A, Kumar A, Pal J. | 04/15/2017 |
| Infection-associated functions of HRI (an eIF2alpha kinase) are independent of its activity as a regulator of protein synthesis. | The host-encoded Heme Regulated Inhibitor (HRI) facilitates virulence-associated activities of bacterial pathogens.
Shrestha N, Boucher J, Bahnan W, Clark ES, Rosqvist R, Fields KA, Khan WN, Schesser K., Free PMC Article | 04/5/2014 |
| During lead-stress, the regulation of hHRI mRNA translation is mediated through its 5'-untranslated region (UTR) that interacts with specific trans-acting factors. | Vimentin is a component of a complex that binds to the 5'-UTR of human heme-regulated eIF2α kinase mRNA and regulates its translation.
Chatterjee S, Panda AC, Berwal SK, Sreejith RK, Ritvika C, Seshadri V, Pal JK. | 04/13/2013 |
| Dephosphorylation of eIF2alpha, specifically in the cortex, is both correlated with and necessary for normal memory consolidation. | Blocking the eIF2α kinase (PKR) enhances positive and negative forms of cortex-dependent taste memory.
Stern E, Chinnakkaruppan A, David O, Sonenberg N, Rosenblum K., Free PMC Article | 04/6/2013 |
| Observational study of gene-disease association. (HuGE Navigator) | See all PubMed (2) articlesAssociation of genetic variants with hemorrhagic stroke in Japanese individuals.
Yoshida T, Kato K, Yokoi K, Oguri M, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nozawa Y, Yamada Y. Assessment of a polymorphism of SDK1 with hypertension in Japanese Individuals.
Oguri M, Kato K, Yokoi K, Yoshida T, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Nozawa Y, Yamada Y. | 12/2/2009 |
| These data establish for the first time, the possible mechanisms of regulation of hHRI gene expression under normal physiological condition, hemin exposure and stress. | Stress-induced overexpression of the heme-regulated eIF-2alpha kinase is regulated by Elk-1 activated through ERK pathway.
Singh VB, Pavithra L, Chattopadhyay S, Pal JK. | 01/21/2010 |
| autophosphorylation of Thr485 is essential for the hyperphosphorylation and activation of HRI and is required for the acquisition of the eIF2alpha kinase activity | Autophosphorylation of threonine 485 in the activation loop is essential for attaining eIF2alpha kinase activity of HRI.
Rafie-Kolpin M, Han AP, Chen JJ. | 01/21/2010 |