A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress - PubMed (original) (raw)
. 2005 Feb 11;307(5711):935-9.
doi: 10.1126/science.1101902.
Affiliations
- PMID: 15705855
- DOI: 10.1126/science.1101902
Free article
A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress
Michael Boyce et al. Science. 2005.
Free article
Abstract
Most protein phosphatases have little intrinsic substrate specificity, making selective pharmacological inhibition of specific dephosphorylation reactions a challenging problem. In a screen for small molecules that protect cells from endoplasmic reticulum (ER) stress, we identified salubrinal, a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha). Salubrinal also blocks eIF2alpha dephosphorylation mediated by a herpes simplex virus protein and inhibits viral replication. These results suggest that selective chemical inhibitors of eIF2alpha dephosphorylation may be useful in diseases involving ER stress or viral infection. More broadly, salubrinal demonstrates the feasibility of selective pharmacological targeting of cellular dephosphorylation events.
Similar articles
- Experimental Evidence Shows Salubrinal, an eIF2α Dephosphorylation Inhibitor, Reduces Xenotoxicant-Induced Cellular Damage.
Matsuoka M, Komoike Y. Matsuoka M, et al. Int J Mol Sci. 2015 Jul 17;16(7):16275-87. doi: 10.3390/ijms160716275. Int J Mol Sci. 2015. PMID: 26193263 Free PMC article. Review. - Enhanced signaling downstream of ribonucleic Acid-activated protein kinase-like endoplasmic reticulum kinase potentiates lipotoxic endoplasmic reticulum stress in human islets.
Ladrière L, Igoillo-Esteve M, Cunha DA, Brion JP, Bugliani M, Marchetti P, Eizirik DL, Cnop M. Ladrière L, et al. J Clin Endocrinol Metab. 2010 Mar;95(3):1442-9. doi: 10.1210/jc.2009-2322. Epub 2010 Jan 15. J Clin Endocrinol Metab. 2010. PMID: 20080856 - Enhancement of cisplatin cytotoxicity by SAHA involves endoplasmic reticulum stress-mediated apoptosis in oral squamous cell carcinoma cells.
Suzuki M, Endo M, Shinohara F, Echigo S, Rikiishi H. Suzuki M, et al. Cancer Chemother Pharmacol. 2009 Nov;64(6):1115-22. doi: 10.1007/s00280-009-0969-x. Epub 2009 Mar 11. Cancer Chemother Pharmacol. 2009. PMID: 19280190 - Effects of salubrinal on cadmium-induced apoptosis in HK-2 human renal proximal tubular cells.
Komoike Y, Inamura H, Matsuoka M. Komoike Y, et al. Arch Toxicol. 2012 Jan;86(1):37-44. doi: 10.1007/s00204-011-0742-x. Epub 2011 Aug 2. Arch Toxicol. 2012. PMID: 21809093 - Targeting phosphorylation of eukaryotic initiation factor-2α to treat human disease.
Fullwood MJ, Zhou W, Shenolikar S. Fullwood MJ, et al. Prog Mol Biol Transl Sci. 2012;106:75-106. doi: 10.1016/B978-0-12-396456-4.00005-5. Prog Mol Biol Transl Sci. 2012. PMID: 22340715 Review.
Cited by
- Histone deacetylases: potential therapeutic targets in cisplatin-induced acute kidney injury.
Guo S, Zhao J, Zhang Y, Qin Y, Yuan J, Yu Z, Xing Y, Zhang Y, Hui Y, Wang A, Han M, Zhao Y, Ning X, Sun S. Guo S, et al. Ann Med. 2024 Dec;56(1):2418958. doi: 10.1080/07853890.2024.2418958. Epub 2024 Oct 25. Ann Med. 2024. PMID: 39450927 Free PMC article. Review. - Interleukin-1 receptor-associated kinase-2 (IRAK2) is a critical mediator of endoplasmic reticulum (ER) stress signaling.
Benosman S, Ravanan P, Correa RG, Hou YC, Yu M, Gulen MF, Li X, Thomas J, Cuddy M, Matsuzawa Y, Sano R, Diaz P, Matsuzawa S, Reed JC. Benosman S, et al. PLoS One. 2013 May 28;8(5):e64256. doi: 10.1371/journal.pone.0064256. Print 2013. PLoS One. 2013. PMID: 23724040 Free PMC article. - Discovery of Sulfonamidebenzamides as Selective Apoptotic CHOP Pathway Activators of the Unfolded Protein Response.
Flaherty DP, Miller JR, Garshott DM, Hedrick M, Gosalia P, Li Y, Milewski M, Sugarman E, Vasile S, Salaniwal S, Su Y, Smith LH, Chung TD, Pinkerton AB, Aubé J, Callaghan MU, Golden JE, Fribley AM, Kaufman RJ. Flaherty DP, et al. ACS Med Chem Lett. 2014 Oct 29;5(12):1278-1283. doi: 10.1021/ml5003234. eCollection 2014 Dec 11. ACS Med Chem Lett. 2014. PMID: 25530830 Free PMC article. - Amino acid substitutions in the non-structural proteins 4A or 4B modulate the induction of autophagy in West Nile virus infected cells independently of the activation of the unfolded protein response.
Blázquez AB, Martín-Acebes MA, Saiz JC. Blázquez AB, et al. Front Microbiol. 2015 Jan 15;5:797. doi: 10.3389/fmicb.2014.00797. eCollection 2014. Front Microbiol. 2015. PMID: 25642225 Free PMC article. - Development of Therapeutics for C9ORF72 ALS/FTD-Related Disorders.
Mis MSC, Brajkovic S, Tafuri F, Bresolin N, Comi GP, Corti S. Mis MSC, et al. Mol Neurobiol. 2017 Aug;54(6):4466-4476. doi: 10.1007/s12035-016-9993-0. Epub 2016 Jun 28. Mol Neurobiol. 2017. PMID: 27349438 Review.
Publication types
MeSH terms
Substances
Grants and funding
- AI19838/AI/NIAID NIH HHS/United States
- AI26077/AI/NIAID NIH HHS/United States
- DDK42394/DK/NIDDK NIH HHS/United States
- DK47119/DK/NIDDK NIH HHS/United States
- ES08681/ES/NIEHS NIH HHS/United States
- GM64703/GM/NIGMS NIH HHS/United States
- NS35138/NS/NINDS NIH HHS/United States
- R37-AG012859/AG/NIA NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases