{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:48:14Z","timestamp":1785433694829,"version":"3.56.0"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["15K09787"],"award-info":[{"award-number":["15K09787"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"award":["15K09787"],"award-info":[{"award-number":["15K09787"]}],"id":[{"id":"https:\/\/ror.org\/048rj2z13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Imiquimod-induced skin inflammation is the most widely used psoriasis mouse model. Although p38 mitogen-activated protein kinase reportedly plays a role in the pathogenesis of psoriatic inflammation, the purpose of one of its upstream activators, apoptosis signal-regulating kinase 1 (ASK1), remains unclear. This study investigated the role of ASK1 and its molecular mechanism in the imiquimod-induced psoriasis model. Compared to wild-type mice, the ASK1 knockout (KO) mouse skin lesion showed a higher clinical score and a thicker epidermis. The mRNA expression of pro-inflammatory cytokines, such as IL-17 and TNF-\u03b1, was also higher. Notably, the expression of aryl hydrocarbon receptor (AhR), a sensor for xenobiotic chemicals that is expressed in the skin to strengthen the skin barrier and accelerate terminal differentiation of the epidermis\u2014as well as its downstream molecule CYP1A1, but not NRF2\u2014was increased in the ASK1 KO psoriatic skin lesion. Immunoprecipitation analysis, followed by Western blotting, revealed that ASK1 interacts with AhR in cells transfected with their respective expression vectors, potentially leading to reduced AhR expression. These results suggest that ASK1 negatively regulates the development of the imiquimod-induced mouse psoriasis model by interacting with AhR and presumably antagonizing the AhR-CYP1A1 axis.<\/jats:p>","DOI":"10.3390\/cimb48070653","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:04:47Z","timestamp":1783418687000},"page":"653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulation of Imiquimod-Induced Mouse Psoriasis Development via Apoptosis Signal-Regulating Kinase 1 Potentially by Antagonizing Aryl Hydrocarbon Receptor Expression"],"prefix":"10.3390","volume":"48","author":[{"given":"Hideaki","family":"Hasegawa","sequence":"first","affiliation":[{"name":"Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruma","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3493-1172","authenticated-orcid":false,"given":"Yasuhiro","family":"Katahira","sequence":"additional","affiliation":[{"name":"Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izuru","family":"Mizoguchi","sequence":"additional","affiliation":[{"name":"Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Mizugami","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-8026","authenticated-orcid":false,"given":"Isao","family":"Naguro","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Ichijo","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9059-4097","authenticated-orcid":false,"given":"Kazutoshi","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9526-1259","authenticated-orcid":false,"given":"Yukari","family":"Okubo","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Shinjuku-ku, Tokyo 160-0023, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-0341","authenticated-orcid":false,"given":"Takayuki","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Department of Immunoregulation, Institute of Medical Science, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Man, A.M., Orasan, M.S., Hoteiuc, O.A., Olanescu-Vaida-Voevod, M.C., and Mocan, T. (2023). Inflammation and Psoriasis: A Comprehensive Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216095"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-032713-120225","article-title":"Immunology of psoriasis","volume":"32","author":"Lowes","year":"2014","journal-title":"Annu. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1146\/annurev-pathol-011811-132448","article-title":"Psoriasis","volume":"7","author":"Perera","year":"2012","journal-title":"Annu. Rev. Pathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/jid.2012.339","article-title":"Global epidemiology of psoriasis: A systematic review of incidence and prevalence","volume":"133","author":"Parisi","year":"2013","journal-title":"J. Investig. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41419-022-04523-3","article-title":"Advances in the pathogenesis of psoriasis: From keratinocyte perspective","volume":"13","author":"Zhou","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/jid.2011.24","article-title":"TNF-alpha downregulates filaggrin and loricrin through c-Jun N-terminal kinase: Role for TNF-alpha antagonists to improve skin barrier","volume":"131","author":"Kim","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41572-025-00630-5","article-title":"Psoriasis","volume":"11","author":"Armstrong","year":"2025","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5836","DOI":"10.4049\/jimmunol.0802999","article-title":"Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23\/IL-17 axis","volume":"182","author":"Mourits","year":"2009","journal-title":"J. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"122991","DOI":"10.1016\/j.lfs.2024.122991","article-title":"Advances in psoriasis research: From pathogenesis to therapeutics","volume":"355","author":"Sugumaran","year":"2024","journal-title":"Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"115429","DOI":"10.1016\/j.intimp.2025.115429","article-title":"Advancing insights into psoriasis: From pathogenesis to current and emerging therapies","volume":"165","author":"Goncalves","year":"2025","journal-title":"Int. Immunopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jdermsci.2013.04.028","article-title":"The role of IL-22 and Th22 cells in human skin diseases","volume":"72","author":"Fujita","year":"2013","journal-title":"J. Dermatol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e71","DOI":"10.1002\/cpim.71","article-title":"IL-23- and Imiquimod-Induced Models of Experimental Psoriasis in Mice","volume":"125","author":"Singh","year":"2019","journal-title":"Curr. Protoc. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41580-020-00322-w","article-title":"Diversity and versatility of p38 kinase signalling in health and disease","volume":"22","author":"Canovas","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1002\/mog2.53","article-title":"p38 mitogen-activated protein kinase: Functions and targeted therapy in diseases","volume":"2","author":"Zheng","year":"2023","journal-title":"MedComm-Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1365-2133.2004.06304.x","article-title":"The mitogen-activated protein kinases p38 and ERK1\/2 are increased in lesional psoriatic skin","volume":"152","author":"Johansen","year":"2005","journal-title":"Br. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1111\/j.1365-2133.2012.10939.x","article-title":"Inhibition of p38 kinase suppresses the development of psoriasis-like lesions in a human skin transplant model of psoriasis","volume":"167","author":"Mihara","year":"2012","journal-title":"Br. J. Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.jaci.2019.06.019","article-title":"Cutaneous p38 mitogen-activated protein kinase activation triggers psoriatic dermatitis","volume":"144","author":"Sakurai","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/s42003-024-06700-w","article-title":"p38alpha deficiency ameliorates psoriasis development by downregulating STAT3-mediated keratinocyte proliferation and cytokine production","volume":"7","author":"Zheng","year":"2024","journal-title":"Commun. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1016\/j.bbagen.2016.09.028","article-title":"Pleiotropic properties of ASK1","volume":"1861","author":"Sakauchi","year":"2017","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5267","DOI":"10.1007\/s11010-025-05330-y","article-title":"Updated Insights on ASK1 Signaling: Mechanisms, regulation, and therapeutic potential in diseases","volume":"480","author":"Thakur","year":"2025","journal-title":"Mol. Cell. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1126\/science.275.5296.90","article-title":"Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK\/JNK and p38 signaling pathways","volume":"275","author":"Ichijo","year":"1997","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1089\/15230860260196218","article-title":"Physiological roles of ASK1-mediated signal transduction in oxidative stress- and endoplasmic reticulum stress-induced apoptosis: Advanced findings from ASK1 knockout mice","volume":"4","author":"Matsuzawa","year":"2002","journal-title":"Antioxid. Redox Signal"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1074\/jbc.M003425200","article-title":"Apoptosis signal-regulating kinase 1 (ASK1) is an intracellular inducer of keratinocyte differentiation","volume":"276","author":"Sayama","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1002\/eji.200425827","article-title":"New mechanisms of skin innate immunity: ASK1-mediated keratinocyte differentiation regulates the expression of beta-defensins, LL37, and TLR2","volume":"35","author":"Sayama","year":"2005","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1177\/12034754241239050","article-title":"The Role of Aryl Hydrocarbon Receptor in the Pathogenesis and Treatment of Psoriasis","volume":"28","author":"Lin","year":"2024","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1002\/eji.201546070","article-title":"AhR modulates the IL-22-producing cell proliferation\/recruitment in imiquimod-induced psoriasis mouse model","volume":"46","author":"Cochez","year":"2016","journal-title":"Eur. J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Furue, M., Hashimoto-Hachiya, A., and Tsuji, G. (2019). Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215424"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/exd.12350","article-title":"Increased expression of the aryl hydrocarbon receptor in patients with chronic inflammatory skin diseases","volume":"23","author":"Kim","year":"2014","journal-title":"Exp. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kim, H.R., Kang, S.Y., Kim, H.O., Park, C.W., and Chung, B.Y. (2020). Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062195"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ogawa, T., and Ishitsuka, Y. (2022). The Role of KEAP1-NRF2 System in Atopic Dermatitis and Psoriasis. Antioxidants, 11.","DOI":"10.3390\/antiox11071397"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/j.jid.2020.11.024","article-title":"CYP1A1 Enzymatic Activity Influences Skin Inflammation Via Regulation of the AHR Pathway","volume":"141","author":"Kyoreva","year":"2021","journal-title":"J. Investig. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2014.04.019","article-title":"Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions","volume":"40","author":"Duarte","year":"2014","journal-title":"Immunity"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1016\/j.jid.2017.05.004","article-title":"Tapinarof Is a Natural AhR Agonist that Resolves Skin Inflammation in Mice and Humans","volume":"137","author":"Smith","year":"2017","journal-title":"J. Investig. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaci.2023.12.013","article-title":"Tapinarof validates the aryl hydrocarbon receptor as a therapeutic target: A clinical review","volume":"154","author":"Silverberg","year":"2024","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"360","DOI":"10.5021\/ad.2020.32.5.360","article-title":"2,3,7,8-Tetrachlorodibenzo-p-Dioxin Regulates the Expression of Aryl Hydrocarbon Receptor-Related Factors and Cytokines in Peripheral Blood Mononuclear Cells and CD4+ T cells from Patients with Atopic Dermatitis and Psoriasis","volume":"32","author":"Um","year":"2020","journal-title":"Ann. Dermatol."},{"key":"ref_37","first-page":"4694","article-title":"A survey of transformation markers in differentiating epidermal cell lines in culture","volume":"40","author":"Yuspa","year":"1980","journal-title":"Cancer Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/carcin\/17.3.435","article-title":"Autoregulation of human CYP1A1 gene promotor activity in HepG2 and MCF-7 cells","volume":"17","author":"Jorgensen","year":"1996","journal-title":"Carcinogenesis"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Zhang, Q.S., Kurpad, D.S., Mahoney, M.G., Steinbeck, M.J., and Freeman, T.A. (2017). Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0185803"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"434","DOI":"10.2183\/pjab.88.434","article-title":"Therapeutic targets in the ASK1-dependent stress signaling pathways","volume":"88","author":"Hayakawa","year":"2012","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hammouda, M.B., Ford, A.E., Liu, Y., and Zhang, J.Y. (2020). The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer. Cells, 9.","DOI":"10.3390\/cells9040857"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1515\/med-2018-0029","article-title":"MAPK Pathway Involved in Epidermal Terminal Differentiation of Normal Human Epidermal Keratinocytes","volume":"13","author":"Meng","year":"2018","journal-title":"Open Med. (Wars)"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Pua, L.J.W., Mai, C.W., Chung, F.F., Khoo, A.S., Leong, C.O., Lim, W.M., and Hii, L.W. (2022). Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031108"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1046\/j.1523-1747.2003.12120.x","article-title":"p38 Mitogen-activated protein kinases on the body surface\u2014A function for p38 delta","volume":"120","author":"Eckert","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1038\/jid.2010.108","article-title":"PKC-delta and -eta, MEKK-1, MEK-6, MEK-3, and p38-delta are essential mediators of the response of normal human epidermal keratinocytes to differentiating agents","volume":"130","author":"Adhikary","year":"2010","journal-title":"J. Investig. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20530","DOI":"10.1074\/jbc.M602712200","article-title":"Inhibition of JNK promotes differentiation of epidermal keratinocytes","volume":"281","author":"Gazel","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kim, H.B., Um, J.Y., Chung, B.Y., Kim, J.C., Kang, S.Y., Park, C.W., and Kim, H.O. (2022). Aryl Hydrocarbon Receptors: Evidence of Therapeutic Targets in Chronic Inflammatory Skin Diseases. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051087"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ishii, T., Warabi, E., and Mann, G.E. (2023). Stress Activated MAP Kinases and Cyclin-Dependent Kinase 5 Mediate Nuclear Translocation of Nrf2 via Hsp90alpha-Pin1-Dynein Motor Transport Machinery. Antioxidants, 12.","DOI":"10.3390\/antiox12020274"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/s41392-025-02500-8","article-title":"The aryl hydrocarbon receptor: Structure, signaling, physiology and pathology","volume":"11","author":"Coumoul","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"101530","DOI":"10.1016\/j.redox.2020.101530","article-title":"The aryl hydrocarbon receptor as a target of environmental stressors\u2014Implications for pollution mediated stress and inflammatory responses","volume":"34","author":"Vogel","year":"2020","journal-title":"Redox Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1093\/toxsci\/kfg083","article-title":"Erk activation is required for Nrf2 nuclear localization during pyrrolidine dithiocarbamate induction of glutamate cysteine ligase modulatory gene expression in HepG2 cells","volume":"73","author":"Zipper","year":"2003","journal-title":"Toxicol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.arcmed.2020.04.015","article-title":"P38 MAPK and Nrf2 Activation Mediated Naked Gold Nanoparticle Induced Heme Oxygenase-1 Expression in Rat Aortic Vascular Smooth Muscle Cells","volume":"51","author":"Ko","year":"2020","journal-title":"Arch. Med. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"120111","DOI":"10.1016\/j.lfs.2021.120111","article-title":"Nrf2\/Keap1\/ARE signaling: Towards specific regulation","volume":"291","author":"Ulasov","year":"2022","journal-title":"Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.jgr.2016.07.003","article-title":"Induction of Nrf2\/ARE-mediated cytoprotective genes by red ginseng oil through ASK1-MKK4\/7-JNK and p38 MAPK signaling pathways in HepG2 cells","volume":"40","author":"Bak","year":"2016","journal-title":"J. Ginseng Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bahman, F., Choudhry, K., Al-Rashed, F., Al-Mulla, F., Sindhu, S., and Ahmad, R. (2024). Aryl hydrocarbon receptor: Current perspectives on key signaling partners and immunoregulatory role in inflammatory diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1421346"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1093\/embo-reports\/kve046","article-title":"ASK1 is required for sustained activations of JNK\/p38 MAP kinases and apoptosis","volume":"2","author":"Tobiume","year":"2001","journal-title":"EMBO Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.molcel.2009.10.016","article-title":"Ubiquitin-like sequence in ASK1 plays critical roles in the recognition and stabilization by USP9X and oxidative stress-induced cell death","volume":"36","author":"Nagai","year":"2009","journal-title":"Mol. Cell"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T11:47:02Z","timestamp":1783424822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/48\/7\/653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":57,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cimb48070653"],"URL":"https:\/\/doi.org\/10.3390\/cimb48070653","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]}}}