ASK1

Summary

Gene Symbol: ASK1
Description: mitogen-activated protein kinase kinase kinase 5
Alias: ASK1, MAPKKK5, MEKK5, mitogen-activated protein kinase kinase kinase 5, ASK-1, MAP/ERK kinase kinase 5, MAPK/ERK kinase kinase 5, MEK kinase 5, MEKK 5, apoptosis signal-regulating kinase 1
Species: human
Products:     ASK1

Top Publications

  1. Takekawa M, Tatebayashi K, Saito H. Conserved docking site is essential for activation of mammalian MAP kinase kinases by specific MAP kinase kinase kinases. Mol Cell. 2005;18:295-306 pubmed
    ..The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAPKKKs), including MTK1 (MEKK4), ASK1, TAK1, TAO2, MEKK1, and Raf-1...
  2. Geleziunas R, Xu W, Takeda K, Ichijo H, Greene W. HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell. Nature. 2001;410:834-8 pubmed
    ..Here we show that HIV-1 Nef associates with and inhibits apoptosis signal-regulating kinase 1 (ASK1), a serine/threonine kinase that forms a common and key signalling intermediate in the Fas and tumour-necrosis ..
  3. Won M, Park K, Byun H, Sohn K, Kim Y, Jeon J, et al. Novel anti-apoptotic mechanism of A20 through targeting ASK1 to suppress TNF-induced JNK activation. Cell Death Differ. 2010;17:1830-41 pubmed publisher
    ..apoptosis through suppression of c-jun N-terminal kinase (JNK) by targeting apoptosis signal-regulating kinase1 (ASK1)...
  4. Takeda K, Noguchi T, Naguro I, Ichijo H. Apoptosis signal-regulating kinase 1 in stress and immune response. Annu Rev Pharmacol Toxicol. 2008;48:199-225 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase of the c-Jun N-terminal kinase (JNK) and p38 MAPK pathways...
  5. Liu Y, Min W. Thioredoxin promotes ASK1 ubiquitination and degradation to inhibit ASK1-mediated apoptosis in a redox activity-independent manner. Circ Res. 2002;90:1259-66 pubmed
    ..has been shown that thioredoxin (Trx) in a reduced form binds to and inhibits apoptosis signal-regulating kinase 1 (ASK1)...
  6. Gao Y, Han C, Huang H, Xin Y, Xu Y, Luo L, et al. Heat shock protein 70 together with its co-chaperone CHIP inhibits TNF-alpha induced apoptosis by promoting proteasomal degradation of apoptosis signal-regulating kinase1. Apoptosis. 2010;15:822-33 pubmed publisher
    ..Our study demonstrated that HSP70 physically interacted with ASK1 and promoted the ubiquitin-dependent proteasomal degradation of ASK1...
  7. Philippe L, Alsaleh G, Pichot A, Ostermann E, Zuber G, Frisch B, et al. MiR-20a regulates ASK1 expression and TLR4-dependent cytokine release in rheumatoid fibroblast-like synoviocytes. Ann Rheum Dis. 2013;72:1071-9 pubmed publisher
    ..Evaluation of miR-20a and ASK1 mRNA was performed by RT-qPCR. ASK1 protein expression was assessed by western blotting...
  8. Kim A, Khursigara G, Sun X, Franke T, Chao M. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol Cell Biol. 2001;21:893-901 pubmed
    ..Here we describe a novel functional interaction between Akt and apoptosis signal-regulating kinase 1 (ASK1), a mitogen-activated protein kinase kinase kinase...
  9. Song J, Rhee J, Suntharalingam M, Walsh S, Spitz D, Lee Y. Role of glutaredoxin in metabolic oxidative stress. Glutaredoxin as a sensor of oxidative stress mediated by H2O2. J Biol Chem. 2002;277:46566-75 pubmed
    ..Deletion mutants showed the C-terminal portion of apoptosis signal-regulating kinase 1 (ASK1) bound GRX, and glucose deprivation disrupted binding...

More Information

Publications80

  1. Shiizaki S, Naguro I, Ichijo H. Activation mechanisms of ASK1 in response to various stresses and its significance in intracellular signaling. Adv Biol Regul. 2013;53:135-44 pubmed publisher
    Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase family...
  2. Subramanian R, Zhang H, Wang H, Ichijo H, Miyashita T, Fu H. Interaction of apoptosis signal-regulating kinase 1 with isoforms of 14-3-3 proteins. Exp Cell Res. 2004;294:581-91 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a critical mediator of apoptotic signaling pathways initiated by a variety of death stimuli...
  3. Takeda K, Hatai T, Hamazaki T, Nishitoh H, Saitoh M, Ichijo H. Apoptosis signal-regulating kinase 1 (ASK1) induces neuronal differentiation and survival of PC12 cells. J Biol Chem. 2000;275:9805-13 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase that activates the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase signaling cascades...
  4. Zhang R, Zhang H, Lin Y, Li J, Pober J, Min W. RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation. J Biol Chem. 2007;282:14788-96 pubmed
    Previously, we have shown that ASK1-interacting protein 1 (AIP1, also known as DAB2IP), a novel member of the Ras-GAP (Ras-GTPase-activating protein) protein family, opens its conformation in response to tumor necrosis factor (TNF), ..
  5. Noguchi T, Ishii K, Fukutomi H, Naguro I, Matsuzawa A, Takeda K, et al. Requirement of reactive oxygen species-dependent activation of ASK1-p38 MAPK pathway for extracellular ATP-induced apoptosis in macrophage. J Biol Chem. 2008;283:7657-65 pubmed publisher
    ..We also found that ATP-induced apoptosis were diminished in ASK1-deficient macrophages accompanied by the lack of p38 activation...
  6. Takizawa T, Tatematsu C, Nakanishi Y. Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1. Implications for apoptosis signaling pathways. Eur J Biochem. 2002;269:6126-32 pubmed
    ..Here we showed a novel interaction between PKR and apoptosis signal-regulating kinase 1 (ASK1), one of the members of the mitogen-activated protein kinase kinase kinase family, which is activated in response ..
  7. Tzeng H, Tsai C, Chang Z, Su C, Wang S, Hwang W, et al. Interleukin-6 induces vascular endothelial growth factor expression and promotes angiogenesis through apoptosis signal-regulating kinase 1 in human osteosarcoma. Biochem Pharmacol. 2013;85:531-40 pubmed publisher
    ..The apoptosis signal-regulating kinase 1 (ASK1)/p38/AP-1 pathway was activated after IL-6 treatment, and IL-6-induced VEGF expression was abolished by the ..
  8. Imoto K, Kukidome D, Nishikawa T, Matsuhisa T, Sonoda K, Fujisawa K, et al. Impact of mitochondrial reactive oxygen species and apoptosis signal-regulating kinase 1 on insulin signaling. Diabetes. 2006;55:1197-204 pubmed
    ..could increase mitochondrial reactive oxygen species (ROS) production, and apoptosis signal-regulating kinase 1 (ASK1) was reported to be required for TNF-alpha-induced apoptosis...
  9. Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, et al. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science. 1997;275:90-4 pubmed
    ..A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/..
  10. Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y, et al. Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 1998;17:2596-606 pubmed
    ..pathways and is required for tumor necrosis factor (TNF)-alpha-induced apoptosis; however, the mechanism regulating ASK1 activity is unknown...
  11. Chen J, Fujii K, Zhang L, Roberts T, Fu H. Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism. Proc Natl Acad Sci U S A. 2001;98:7783-8 pubmed
    ..We found that Raf-1 interacts with the proapoptotic, stress-activated protein kinase ASK1 (apoptosis signal-regulating kinase 1) in vitro and in vivo...
  12. Stark M, Woods S, Gartside M, Bonazzi V, Dutton Regester K, Aoude L, et al. Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing. Nat Genet. 2011;44:165-9 pubmed publisher
    ..Attenuation of MAP3K9 function in melanoma cells using siRNA led to increased cell viability after temozolomide treatment, suggesting that decreased MAP3K pathway activity can lead to chemoresistance in melanoma. ..
  13. Yang T, Lai C, Shiu S, Chuang P, Tzou B, Lin Y, et al. Japanese encephalitis virus down-regulates thioredoxin and induces ROS-mediated ASK1-ERK/p38 MAPK activation in human promonocyte cells. Microbes Infect. 2010;12:643-51 pubmed publisher
    ..JEV infection caused increased intracellular ROS production and activation of ASK1-ERK/p38 MAPK signaling. ERK/p38 MAPK inhibitor PD98059 treatment definitely suppressed this apoptosis...
  14. Chang H, Nishitoh H, Yang X, Ichijo H, Baltimore D. Activation of apoptosis signal-regulating kinase 1 (ASK1) by the adapter protein Daxx. Science. 1998;281:1860-3 pubmed
    ..Daxx was found to activate the JNK kinase kinase ASK1, and overexpression of a kinase-deficient ASK1 mutant inhibited Fas- and Daxx-induced apoptosis and JNK activation...
  15. Nishitoh H, Saitoh M, Mochida Y, Takeda K, Nakano H, Rothe M, et al. ASK1 is essential for JNK/SAPK activation by TRAF2. Mol Cell. 1998;2:389-95 pubmed
    ..The apoptosis signal-regulating kinase 1 (ASK1) is activated by TNF and stimulates JNK activation...
  16. Zhang R, Luo D, Miao R, Bai L, Ge Q, Sessa W, et al. Hsp90-Akt phosphorylates ASK1 and inhibits ASK1-mediated apoptosis. Oncogene. 2005;24:3954-63 pubmed
    Hsp90 client protein Akt has been shown to inhibit cell apoptosis in part by inhibiting proapoptotic kinase ASK1 (apoptosis signal-regulating kinase 1) activity...
  17. Seong H, Jung H, Ichijo H, Ha H. Reciprocal negative regulation of PDK1 and ASK1 signaling by direct interaction and phosphorylation. J Biol Chem. 2010;285:2397-414 pubmed publisher
    ..association between PDK1 (3-phosphoinositide-dependent protein kinase 1), a critical mediator of cell survival, and ASK1 (apoptosis signal-regulating kinase 1), an apoptotic stress-activated MAPKKK...
  18. Bunkoczi G, Salah E, Filippakopoulos P, Fedorov O, Muller S, Sobott F, et al. Structural and functional characterization of the human protein kinase ASK1. Structure. 2007;15:1215-26 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) plays an essential role in stress and immune response and has been linked to the development of several diseases...
  19. Fujii K, Goldman E, Park H, Zhang L, Chen J, Fu H. Negative control of apoptosis signal-regulating kinase 1 through phosphorylation of Ser-1034. Oncogene. 2004;23:5099-104 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a serine/threonine kinase that mediates cell stress signaling initiated by diverse stimuli, such as H(2)O(2) and TNF alpha...
  20. McDonald P, Chow C, Miller W, Laporte S, Field M, Lin F, et al. Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science. 2000;290:1574-7 pubmed
    ..The upstream JNK activators apoptosis signal-regulating kinase 1 (ASK1) and mitogen-activated protein kinase (MAPK) kinase 4 were also found in complex with beta-arrestin 2...
  21. Zhang L, Chen J, Fu H. Suppression of apoptosis signal-regulating kinase 1-induced cell death by 14-3-3 proteins. Proc Natl Acad Sci U S A. 1999;96:8511-5 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component of a signaling pathway induced by many death stimuli, including tumor necrosis factor alpha, Fas, and the anticancer drugs cisplatin and paclitaxel...
  22. Takeda K, Shimozono R, Noguchi T, Umeda T, Morimoto Y, Naguro I, et al. Apoptosis signal-regulating kinase (ASK) 2 functions as a mitogen-activated protein kinase kinase kinase in a heteromeric complex with ASK1. J Biol Chem. 2007;282:7522-31 pubmed
    ..Here we show that ASK2, a highly related serine/threonine kinase to ASK1, also functions as a MAP3K only in a heteromeric complex with ASK1...
  23. Kim E, Noh K, Yoon J, Cho J, Yoon K, Dreyfuss G, et al. Positive regulation of ASK1-mediated c-Jun NH(2)-terminal kinase signaling pathway by the WD-repeat protein Gemin5. Cell Death Differ. 2007;14:1518-28 pubmed
    ..We now show that Gemin5 facilitates the activation of apoptosis signal-regulating kinase 1 (ASK1) and downstream signaling...
  24. Nadeau P, Charette S, Landry J. REDOX reaction at ASK1-Cys250 is essential for activation of JNK and induction of apoptosis. Mol Biol Cell. 2009;20:3628-37 pubmed publisher
    b>ASK1 cysteine oxidation allows JNK activation upon oxidative stress. Trx1 negatively regulates this pathway by reducing the oxidized cysteines of ASK1...
  25. Wang X, Diener K, Jannuzzi D, Trollinger D, Tan T, Lichenstein H, et al. Molecular cloning and characterization of a novel protein kinase with a catalytic domain homologous to mitogen-activated protein kinase kinase kinase. J Biol Chem. 1996;271:31607-11 pubmed
    ..We report herein the isolation of a cDNA encoding a novel protein kinase designated MAPKKK5 from a human macrophage library...
  26. Zhang R, He X, Liu W, Lu M, Hsieh J, Min W. AIP1 mediates TNF-alpha-induced ASK1 activation by facilitating dissociation of ASK1 from its inhibitor 14-3-3. J Clin Invest. 2003;111:1933-43 pubmed
    TNF-alpha activates ASK1 in part by dissociating 14-3-3 from apoptosis signal-regulating kinase 1 (ASK1). In the present study, we identified a novel Ras GTPase-activating protein (Ras-GAP) as an ASK1-interacting protein (AIP1)...
  27. Charette S, Lambert H, Landry J. A kinase-independent function of Ask1 in caspase-independent cell death. J Biol Chem. 2001;276:36071-4 pubmed
    b>Ask1 (apoptosis signal-regulating kinase 1) is activated as a consequence of cell exposure to a variety of stresses and can then initiate apoptosis...
  28. Morita K, Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, et al. Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress. EMBO J. 2001;20:6028-36 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase (MAPKKK) that activates the JNK and p38 MAP kinase cascades and is activated in response to oxidative stress such as hydrogen peroxide (H(2)O(2))...
  29. Min W, Lin Y, Tang S, Yu L, Zhang H, Wan T, et al. AIP1 recruits phosphatase PP2A to ASK1 in tumor necrosis factor-induced ASK1-JNK activation. Circ Res. 2008;102:840-8 pubmed publisher
    ..ASK]1-interacting protein 1), a novel member of the Ras-GAP protein family, facilitates dephosphorylation of ASK1 at pSer967 and subsequently 14-3-3 release from ASK1, leading to enhanced ASK1-JNK signaling...
  30. Kim S, Shim J, Chun E, Lee K. Reciprocal inhibition between the transforming growth factor-?-activated kinase 1 (TAK1) and apoptosis signal-regulating kinase 1 (ASK1) mitogen-activated protein kinase kinase kinases and its suppression by TAK1-binding protein 2 (TAB2), an adapter . J Biol Chem. 2012;287:3381-91 pubmed publisher
    ..transforming growth factor-?-activated kinase 1 (TAK1)-TAK1-binding protein 1 (TAB1) complex negatively regulates ASK1-mediated signaling, and TAB2 reciprocally regulates TAK1-induced NF-?B and apoptosis signal-regulating kinase 1 (..
  31. Arning L, Monte D, Hansen W, Wieczorek S, Jagiello P, Akkad D, et al. ASK1 and MAP2K6 as modifiers of age at onset in Huntington's disease. J Mol Med (Berl). 2008;86:485-90 pubmed publisher
    ..markers revealed consolidated evidence for association in a candidate region comprising the genes MAP3K5 (ASK1)/PEX7 at 6q23.3 and in the gene MAP2K6 at 17q24.3...
  32. Zou X, Tsutsui T, Ray D, Blomquist J, Ichijo H, Ucker D, et al. The cell cycle-regulatory CDC25A phosphatase inhibits apoptosis signal-regulating kinase 1. Mol Cell Biol. 2001;21:4818-28 pubmed
    ..In this study, we have identified apoptosis signal-regulating kinase 1 (ASK1) as a CDC25A-interacting protein by yeast two-hybrid screening...
  33. Tobiume K, Saitoh M, Ichijo H. Activation of apoptosis signal-regulating kinase 1 by the stress-induced activating phosphorylation of pre-formed oligomer. J Cell Physiol. 2002;191:95-104 pubmed
    Apoptosis signal-regulating kinase 1 (ASK1) is a MAPKKK family member which activates c-Jun N-terminal kinase (JNK) and p38. In non-stressed cells, ASK1 exists as an inactive complex with the reduced form of thioredoxin...
  34. Goldman E, Chen L, Fu H. Activation of apoptosis signal-regulating kinase 1 by reactive oxygen species through dephosphorylation at serine 967 and 14-3-3 dissociation. J Biol Chem. 2004;279:10442-9 pubmed
    ..Recent genetic studies have placed apoptosis signal-regulating kinase 1 (ASK1) in a pivotal position in transmitting H(2)O(2)-initiated signals...
  35. Nishitoh H, Matsuzawa A, Tobiume K, Saegusa K, Takeda K, Inoue K, et al. ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 2002;16:1345-55 pubmed
    ..polyQ with pathogenic repeat length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, ..
  36. Hoeflich K, Yeh W, Yao Z, Mak T, Woodgett J. Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1). Oncogene. 1999;18:5814-20 pubmed
    ..We report that TRAF2, TRAF5 and TRAF6 associate with apoptosis signal-regulating kinase 1 (ASK1), and a catalytically-inactive ASK1 mutant blocks stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (..
  37. Hasegawa Y, Toyama K, Uekawa K, Ichijo H, Kim Mitsuyama S. Role of ASK1/p38 Cascade in a Mouse Model of Alzheimer's Disease and Brain Aging. J Alzheimers Dis. 2017;: pubmed publisher
    To examine the role of ASK1 in Alzheimer's disease (AD), we generated 5XFAD mice deficient in ASK1 and investigated the characteristics of old 5XFAD and wild-type mice with ASK1 deficiency...
  38. Shi L, Wang Z, Liu X, Li M, Zhang S, Song X. Bax inhibitor-1 is required for resisting the Early Brain Injury induced by subarachnoid hemorrhage through regulating IRE1-JNK pathway. Neurol Res. 2018;40:189-196 pubmed publisher
    ..receptor-associated factor 2 (TRAF2), and increased the activation levels of apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) in the hippocampus of SAH rats compared with rats in SAH + vehicle group...
  39. Yang M, Yu M, Guan D, Gu J, Cao X, Wang W, et al. ASK1-JNK signaling cascade mediates Ad-ST13-induced apoptosis in colorectal HCT116 cells. J Cell Biochem. 2010;110:581-8 pubmed publisher
    ..Here, we demonstrate that Ad-ST13 (ST13 mediated by adenovirus) activates apoptosis signal-regulated kinase (ASK1) and c-Jun N-terminal kinase (JNK) but not p38 (mitogen-activated protein kinase) in human colorectal HCT116 cells...
  40. Matsuzawa A. Physiological roles of ASK family members in innate immunity and their involvement in pathogenesis of immune diseases. Adv Biol Regul. 2017;66:46-53 pubmed publisher
    ..Recently, we found that ASK1, a member of ASK family, is activated by bacterial components, such as lipopolysaccharide, in a reactive oxygen ..
  41. Menon R, Boldogh I, Urrabaz Garza R, Polettini J, Syed T, Saade G, et al. Senescence of primary amniotic cells via oxidative DNA damage. PLoS ONE. 2013;8:e83416 pubmed publisher
    ..used to determine the changes in mass and post-translational modification of apoptosis signal-regulating kinase (ASK1), phospho-p38 (P-p38 MAPK), and p19(arf)...
  42. Tesch G, Ma F, Nikolic Paterson D. ASK1: a new therapeutic target for kidney disease. Am J Physiol Renal Physiol. 2016;311:F373-81 pubmed publisher
    ..Apoptosis signal-regulating kinase 1 (ASK1) acts as an upstream regulator for the activation of p38 MAPK and JNK in kidney disease...
  43. Chen Y, Hwang S, Chan V, Chung N, Wang S, Li Z, et al. Binding of HIV-1 gp120 to DC-SIGN promotes ASK-1-dependent activation-induced apoptosis of human dendritic cells. PLoS Pathog. 2013;9:e1003100 pubmed publisher
  44. Sekine Y, Hatanaka R, Watanabe T, Sono N, Iemura S, Natsume T, et al. The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5. Mol Cell. 2012;48:692-704 pubmed publisher
    Reactive oxygen species (ROS)-induced activation of Apoptosis signal-regulating kinase 1 (ASK1) plays crucial roles in oxidative stress-mediated cell death through the activation of the JNK and p38 MAPK pathways...
  45. Hassan M, Feyen O, Grinstein E. Fas-induced apoptosis of renal cell carcinoma is mediated by apoptosis signal-regulating kinase 1 via mitochondrial damage-dependent caspase-8 activation. Cell Oncol. 2009;31:437-56 pubmed publisher
    ..The present study shows an essential role for apoptosis signal-regulating kinase 1 (ASK1), together with both c-jun-N-terminal kinase (JNK) and p38 pathways, and caspase-8 in this process...
  46. Yang C, Shin D, Lee H, Son J, Lee S, Akira S, et al. ASK1-p38 MAPK-p47phox activation is essential for inflammatory responses during tuberculosis via TLR2-ROS signalling. Cell Microbiol. 2008;10:741-54 pubmed
    ..PPD-induced ROS production led to robust activation of ASK1 upstream of p38 MAPK, via TLR2...
  47. Ida L, Yamaguchi T, Yanagisawa K, Kajino T, Shimada Y, Suzuki M, et al. Receptor tyrosine kinase-like orphan receptor 1, a target of NKX2-1/TTF-1 lineage-survival oncogene, inhibits apoptosis signal-regulating kinase 1-mediated pro-apoptotic signaling in lung adenocarcinoma. Cancer Sci. 2016;107:155-61 pubmed publisher
    ..pro-survival phosphatidylinositol 3-kinase-protein kinase B and pro-apoptotic apoptosis signal-regulating kinase 1 (ASK1)-p38MAPK signaling...
  48. Leestemaker Y, de Jong A, Witting K, Penning R, Schuurman K, Rodenko B, et al. Proteasome Activation by Small Molecules. Cell Chem Biol. 2017;24:725-736.e7 pubmed publisher
    ..Genetic and chemical inhibition of either p38 MAPK, its upstream regulators, ASK1 and MKK6, and downstream target, MK2, enhance proteasome activity...
  49. Zhang Q, Zhao L, Tian X, Yan C, Li Y, Liu Y, et al. The novel intracellular protein CREG inhibits hepatic steatosis, obesity, and insulin resistance. Hepatology. 2017;66:834-854 pubmed publisher
    ..Mechanistically, CREG interacts directly with apoptosis signal-regulating kinase 1 (ASK1) and inhibits its phosphorylation, thereby blocking the downstream MKK4/7-JNK1 signaling pathway and leading to ..
  50. Watanabe T, Sekine S, Naguro I, Sekine Y, Ichijo H. Apoptosis Signal-regulating Kinase 1 (ASK1)-p38 Pathway-dependent Cytoplasmic Translocation of the Orphan Nuclear Receptor NR4A2 Is Required for Oxidative Stress-induced Necrosis. J Biol Chem. 2015;290:10791-803 pubmed publisher
    ..b>ASK1 is a stress-responsive MAP3K that acts as an upstream kinase of p38 and is activated by various stresses, such as ..
  51. Sumida Y, Yoneda M. Current and future pharmacological therapies for NAFLD/NASH. J Gastroenterol. 2018;53:362-376 pubmed publisher
    ..This class of drug includes apoptosis signaling kinase 1 (ASK1) inhibitor and emricasan (an irreversible caspase inhibitor)...
  52. Zhao N, Mi L, Zhang X, Xu M, Yu H, Liu Z, et al. Enhanced MiR-711 transcription by PPARγ induces endoplasmic reticulum stress-mediated apoptosis targeting calnexin in rat cardiomyocytes after myocardial infarction. J Mol Cell Cardiol. 2018;118:36-45 pubmed publisher
    ..transcription factor (ATF6), spliced X-box binding protein 1 (XBP1), apoptotic signal-regulating kinase 1 (ASK1), CCAAT-enhancer binding protein homologous protein (CHOP), caspase-12, and endoplasmic reticulum oxidoreductase 1 ..
  53. Miyakawa K, Matsunaga S, Kanou K, Matsuzawa A, Morishita R, Kudoh A, et al. ASK1 restores the antiviral activity of APOBEC3G by disrupting HIV-1 Vif-mediated counteraction. Nat Commun. 2015;6:6945 pubmed publisher
    ..We demonstrate here that the host protein ASK1 (apoptosis signal-regulating kinase 1) interferes with the counteraction by Vif and revitalizes A3G-mediated viral ..
  54. Tan J, Zhuang L, Jiang X, Yang K, Karuturi K, Yu Q. Apoptosis signal-regulating kinase 1 is a direct target of E2F1 and contributes to histone deacetylase inhibitor-induced apoptosis through positive feedback regulation of E2F1 apoptotic activity. J Biol Chem. 2006;281:10508-15 pubmed
    ..Data analysis focusing on 220 apoptosis-related genes identified apoptosis signal-regulating kinase 1 (ASK1) as one of a few genes in addition to Bim that are substantially up-regulated by SAHA upon E2F1 activation...
  55. Ji W, Yang M, Praggastis A, Li Y, Zhou H, He Y, et al. Carbamoylating activity associated with the activation of the antitumor agent laromustine inhibits angiogenesis by inducing ASK1-dependent endothelial cell death. PLoS ONE. 2014;9:e103224 pubmed publisher
    ..101MDCE), an analog of laromustine that generates only methyl isocyanate, activates ASK1-JNK/p38 signaling in endothelial cells (EC)...
  56. Tafrali C, Paizi A, Borg J, Radmilovic M, Bartsakoulia M, Giannopoulou E, et al. Genomic variation in the MAP3K5 gene is associated with ?-thalassemia disease severity and hydroxyurea treatment efficacy. Pharmacogenomics. 2013;14:469-83 pubmed publisher
    ..Lastly, the abovementioned MAP3K5 variants are associated with HU treatment efficacy. Our data suggest that these MAP3K5 variants are indicative of ?-thalassemia disease severity and response to HU treatment. ..
  57. Ko Y, Kang Y, Park H, Seol W, Kim J, Kim T, et al. Apoptosis signal-regulating kinase 1 controls the proapoptotic function of death-associated protein (Daxx) in the cytoplasm. J Biol Chem. 2001;276:39103-6 pubmed
    ..could be determined by the relative concentration of a proapoptotic kinase, apoptosis signal-regulating kinase 1 (ASK1) by using immunofluorescence and transcriptional reporter assay...
  58. Chen M, Hwang M, Chou Y, Chen W, Cheng G, Nakano H, et al. The role of apoptosis signal-regulating kinase 1 in lymphotoxin-beta receptor-mediated cell death. J Biol Chem. 2003;278:16073-81 pubmed
    ..Cross-linking of LTbetaR is able to recruit TRAF3 and TRAF5 to activate ASK1, whereas its activity is inhibited by free radical scavenger carboxyfullerenes...
  59. Donath S, An J, Lee S, Gertz K, Datwyler A, Harms U, et al. Interaction of ARC and Daxx: A Novel Endogenous Target to Preserve Motor Function and Cell Loss after Focal Brain Ischemia in Mice. J Neurosci. 2016;36:8132-48 pubmed publisher
    ..Functionally, TAT.ARC treatment inhibited DAXX-ASK1-JNK signaling in the ischemic brain...
  60. Liu T, Zhou H, Min W. ASK family in cardiovascular biology and medicine. Adv Biol Regul. 2017;66:54-62 pubmed publisher
    ..Apoptosis signal-regulating kinase (ASK) family members ASK1, ASK2 and ASK3 are the key molecules in MAPK signal cascades and are activated by various stresses...
  61. Fujisawa T. Therapeutic application of apoptosis signal-regulating kinase 1 inhibitors. Adv Biol Regul. 2017;66:85-90 pubmed publisher
    Apoptosis signal-regulating kinase 1 (ASK1) is a member of the stress-activated mitogen-activated protein kinase kinase kinase (MAP3K) family...
  62. Jiang W, Zhang Y, Xia Q, Zhu J, Yu X, Fan T, et al. MicroRNA-19a regulates lipopolysaccharide-induced endothelial cell apoptosis through modulation of apoptosis signal-regulating kinase 1 expression. BMC Mol Biol. 2015;16:11 pubmed publisher
    ..endothelial cells from lipopolysaccharide (LPS)-induced apoptosis through the apoptosis signal-regulating kinase 1 (ASK1)/p38 pathway...
  63. Nadeau P, Charette S, Toledano M, Landry J. Disulfide Bond-mediated multimerization of Ask1 and its reduction by thioredoxin-1 regulate H(2)O(2)-induced c-Jun NH(2)-terminal kinase activation and apoptosis. Mol Biol Cell. 2007;18:3903-13 pubmed
    Apoptosis signal-regulated kinase-1 (Ask1) lies upstream of a major redox-sensitive pathway leading to the activation of Jun NH(2)-terminal kinase (JNK) and the induction of apoptosis...
  64. Zhang Q, Kurpad D, Mahoney M, Steinbeck M, Freeman T. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration. PLoS ONE. 2017;12:e0185803 pubmed publisher
    ..Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice ..
  65. Zhang Q, Eaton G, Diallo C, Freeman T. Stress-Induced Activation of Apoptosis Signal-Regulating Kinase 1 Promotes Osteoarthritis. J Cell Physiol. 2016;231:944-53 pubmed publisher
    Apoptosis signal-regulated kinase 1 (ASK1) has been shown to affect a wide range of cellular processes including stress-related responses, cytokine and growth factor signaling, cell cycle and cell death...
  66. Kim H, Oh Y, Kim K, Jeong S, Chon S, Kim D, et al. Cyclophilin A regulates JNK/p38-MAPK signaling through its physical interaction with ASK1. Biochem Biophys Res Commun. 2015;464:112-7 pubmed publisher
    ..In this study, we have demonstrated that CypA regulates apoptosis signaling-regulating kinase 1 (ASK1) through its direct binding...
  67. Tanaka A, Yamamoto A, Murota K, Tsujiuchi T, Iwamori M, Fukushima N. Polyunsaturated fatty acids induce ovarian cancer cell death through ROS-dependent MAP kinase activation. Biochem Biophys Res Commun. 2017;493:468-473 pubmed publisher
    ..A further study of the underlying mechanisms for ROS-dependent cell death induced by PUFAs will lead to the discovery of a new target for cancer therapy or diagnosis. ..
  68. Zama T, Aoki R, Kamimoto T, Inoue K, Ikeda Y, Hagiwara M. Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the JNK signaling pathway. J Biol Chem. 2002;277:23919-26 pubmed
    ..MAPKK kinases (MAPKKKs) revealed that SKRP1 also interacted with the MAPKKK, apoptosis signal-regulating kinase 1 (ASK1), but not with MAP kinase kinase kinase 1 (MEKK1)...
  69. Cho J, Lee M, Yoon K, Lee J, Cho S, Choi E. Arginine methylation-dependent regulation of ASK1 signaling by PRMT1. Cell Death Differ. 2012;19:859-70 pubmed publisher
    ..We now show that PRMT1 methylates apoptosis signal-regulating kinase 1 (ASK1) at arginine residues 78 and 80 and thereby negatively regulates ASK1 signaling...
  70. Mnich S, Blanner P, Hu L, Shaffer A, Happa F, O NEIL S, et al. Critical role for apoptosis signal-regulating kinase 1 in the development of inflammatory K/BxN serum-induced arthritis. Int Immunopharmacol. 2010;10:1170-6 pubmed publisher
    In this report, we show that apoptosis signal-regulating kinase 1(-/-) (ASK1 KO) mice were resistant to inflammatory arthritis induced in the K/BxN serum transfer model of rheumatoid arthritis (RA)...
  71. Xiang M, Wang P, Wang A, Zhang X, Zhang Y, Zhang P, et al. Targeting hepatic TRAF1-ASK1 signaling to improve inflammation, insulin resistance, and hepatic steatosis. J Hepatol. 2016;64:1365-77 pubmed publisher
    ..Mechanistically, hepatocyte TRAF1 promotes hepatic steatosis through enhancing the activation of ASK1-mediated P38/JNK cascades, as evidenced by the fact that ASK1 inhibition abolished the exacerbated effect of TRAF1 ..