{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:13:50Z","timestamp":1790856830924,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T00:00:00Z","timestamp":1563926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["DK60521"],"award-info":[{"award-number":["DK60521"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["DK54733"],"award-info":[{"award-number":["DK54733"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>All-trans retinoic acid (AtRA), an active metabolite of vitamin A, is recognized for its classical action as an endocrine hormone that triggers genomic effects mediated through nuclear receptors RA receptors (RARs). New evidence shows that atRA-mediated cellular responses are biphasic with rapid and delayed responses. Most of these rapid atRA responses are the outcome of its binding to cellular retinoic acid binding protein 1 (CRABP1) that is predominantly localized in cytoplasm and binds to atRA with a high affinity. This review summarizes the most recent studies of such non-genomic outcomes of atRA and the role of CRABP1 in mediating such rapid effects in different cell types. In embryonic stem cells (ESCs), atRA-CRABP1 dampens growth factor sensitivity and stemness. In a hippocampal neural stem cell (NSC) population, atRA-CRABP1 negatively modulates NSC proliferation and affects learning and memory. In cardiomyocytes, atRA-CRABP1 prevents over-activation of calcium-calmodulin-dependent protein kinase II (CaMKII), protecting heart function. These are supported by the fact that CRABP1 gene knockout (KO) mice exhibit multiple phenotypes including hippocampal NSC expansion and spontaneous cardiac hypertrophy. This indicates that more potential processes\/signaling pathways involving atRA-CRABP1 may exist, which remain to be identified.<\/jats:p>","DOI":"10.3390\/ijms20153610","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T10:48:19Z","timestamp":1563965299000},"page":"3610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["All-trans Retinoic Acid as a Versatile Cytosolic Signal Modulator Mediated by CRABP1"],"prefix":"10.3390","volume":"20","author":[{"given":"Isha","family":"Nagpal","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Na","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1038\/219800a0","article-title":"The molecular basis of visual excitation","volume":"219","author":"Wald","year":"1968","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1093\/jn\/131.6.1647","article-title":"The discovery of the visual function of vitamin A","volume":"131","author":"Wolf","year":"2001","journal-title":"J. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/hlca.19310140511","article-title":"Zur Kenntnis des Vitamins-A aus Fischtranen","volume":"14","author":"Karrer","year":"1931","journal-title":"Helv. Chim. Acta"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1021\/ja01289a075","article-title":"The Isolation of Crystalline Vitamin A1","volume":"59","author":"Holmes","year":"1937","journal-title":"J. Am. Chem. Soc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1242\/dev.001107","article-title":"Retinoic acid, meiosis and germ cell fate in mammals","volume":"134","author":"Bowles","year":"2007","journal-title":"Development"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/2045-3701-2-11","article-title":"Retinoic acid synthesis and functions in early embryonic development","volume":"2","author":"Kam","year":"2012","journal-title":"Cell Biosci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ca\u00f1ete, A., Cano, E., Mu\u00f1oz-Ch\u00e1puli, R., and Carmona, R. (2017). Role of vitamin a\/retinoic acid in regulation of embryonic and adult hematopoiesis. Nutrients, 9.","DOI":"10.3390\/nu9020159"},{"key":"ref_8","first-page":"1023","article-title":"Vitamin A and Retinoids in Health and Disease","volume":"310","author":"Goodman","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.pharmthera.2019.01.006","article-title":"Vitamin A signaling and homeostasis in obesity, diabetes, and metabolic disorders","volume":"197","author":"Blaner","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"566","DOI":"10.3390\/jcm3020566","article-title":"Clinical Medicine Molecular Mechanisms of Retinoid Receptors in Diabetes-Induced Cardiac Remodeling","volume":"3","author":"Pan","year":"2014","journal-title":"J. Clin. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.bbalip.2011.07.001","article-title":"Retinoid metabolism and its effects on the vasculature","volume":"1821","author":"Rhee","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.bbalip.2011.06.023","article-title":"Hepatic metabolism of retinoids and disease associations","volume":"1821","author":"Shirakami","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Doll\u00e9, P., and Niederreither, K. (2015). The Retinoids: Biology, Biochemistry, and Disease, Wiley Blackwell.","DOI":"10.1002\/9781118628003"},{"key":"ref_14","first-page":"1","article-title":"Retinoids in the pancreas","volume":"5","author":"Brun","year":"2016","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jsbmb.2015.09.036","article-title":"The role of vitamin A and retinoic acid receptor signaling in post-natal maintenance of bone","volume":"155","author":"Green","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_16","unstructured":"Roberts, A.B., Sporn, M.B., and Goodman, D.S. (1994). The retinoid receptors. The Retinoids: Biology, Chemistry and Medicine, Raven Press."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1101\/gad.6.3.329","article-title":"Characterization of three RXR genes that mediate the action of 9-cis retinoic acid","volume":"6","author":"Mangelsdorf","year":"1992","journal-title":"Genes Dev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1096\/fasebj.10.9.8801176","article-title":"A decade of molecular biology of retinoic acid receptors","volume":"10","author":"Chambon","year":"1996","journal-title":"FASEB J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1002\/neu.20242","article-title":"Overview of retinoid metabolism and function","volume":"66","author":"Blomhoff","year":"2006","journal-title":"J. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1146\/annurev-immunol-041015-055427","article-title":"Retinoic Acid and Retinoic Acid Receptors as Pleiotropic Modulators of the Immune System","volume":"34","author":"Larange","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.bbadis.2010.10.007","article-title":"The molecular physiology of nuclear retinoic acid receptors. From health to disease","volume":"1812","author":"Duong","year":"2011","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R121","DOI":"10.1530\/EC-17-0101","article-title":"Vitamin A, endocrine tissues and hormones: Interplay and interactions","volume":"6","author":"Brossaud","year":"2017","journal-title":"Endocr. Connect."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11424","DOI":"10.1073\/pnas.0710561105","article-title":"Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression","volume":"105","author":"Gupta","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1002\/stem.623","article-title":"Promyelocytic leukemia protein in retinoic acid-induced chromatin remodeling of Oct4 gene promoter","volume":"29","author":"Chuang","year":"2011","journal-title":"Stem Cells"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/stem.2190","article-title":"Retinoic Acid Induces Ubiquitination-Resistant RIP140\/LSD1 Complex to Fine-Tune Pax6 Gene in Neuronal Differentiation","volume":"34","author":"Wu","year":"2016","journal-title":"Stem Cells"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.cellsig.2012.09.002","article-title":"Cellular retinoic acid binding protein I mediates rapid non-canonical activation of ERK1\/2 by all-trans retinoic acid","volume":"25","author":"Persaud","year":"2013","journal-title":"Cell. Signal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.bmc.2013.11.025","article-title":"Retinoic acid signaling pathways in development and diseases","volume":"22","author":"Das","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1080\/10942910601045271","article-title":"Functional properties of carotenoids in human health","volume":"10","author":"Perera","year":"2007","journal-title":"Int. J. Food Prop."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chelstowska, S., Widjaja-Adhi, M.A.K., Silvaroli, J.A., and Golczak, M. (2016). Molecular basis for vitamin A uptake and storage in vertebrates. Nutrients, 8.","DOI":"10.3390\/nu8110676"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1146\/annurev.nutr.25.050304.092614","article-title":"Mechanisms of Digestion and Absorption of Dietary Vitamin, A","volume":"25","author":"Harrison","year":"2005","journal-title":"Annu. Rev. Nutr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1194\/jlr.R037648","article-title":"Retinol and retinyl esters: Biochemistry and physiology Thematic Review Series: Fat-soluble vitamins: Vitamin, A","volume":"54","author":"Blaner","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3390\/nu3010063","article-title":"Vitamin A metabolism: An update","volume":"3","author":"Clugston","year":"2011","journal-title":"Nutrients"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1152\/physrev.1991.71.4.951","article-title":"Vitamin A metabolism: New perspectives on absorption, transport, and storage","volume":"71","author":"Blomhoff","year":"1991","journal-title":"Physiol. Rev."},{"key":"ref_34","unstructured":"Dolle, P., and Niederreither, K. (2015). Vitamin A Metabolism, Storage and Tissue Delivery Mechanisms. The Retinoids: Biology, Biochemistry, and Disease, Wiley-Blackwell."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"32160","DOI":"10.1074\/jbc.M010086200","article-title":"Expression and characterization of a murine enzyme able to cleave \u03b2-carotene. The formation of retinoids","volume":"276","author":"Paik","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7813","DOI":"10.1007\/s00253-015-6830-8","article-title":"Biochemical properties of retinoid-converting enzymes and biotechnological production of retinoids","volume":"99","author":"Hong","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15886","DOI":"10.1074\/jbc.M111.325142","article-title":"Naturally occurring eccentric cleavage products of provitamin A \u03b2-carotene function as antagonists of retinoic acid receptors","volume":"287","author":"Eroglu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14110","DOI":"10.1074\/jbc.M011510200","article-title":"Identification and Characterization of a Mammalian Enzyme Catalyzing the Asymmetric Oxidative Cleavage of Provitamin A","volume":"276","author":"Kiefer","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1194\/jlr.R039537","article-title":"Carotenoid metabolism in mammals, including man: Formation, occurrence, and function of apocarotenoids thematic review series: Fat-soluble vitamins: Vitamin A","volume":"54","author":"Eroglu","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1194\/jlr.M700263-JLR200","article-title":"Mechanisms of provitamin A (carotenoid) and vitamin A (retinol) transport into and out of intestinal Caco-2 cells","volume":"48","author":"During","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.1021\/bi9927235","article-title":"Hydrolysis of Retinyl Esters by Pancreatic Triglyceride Lipase","volume":"39","author":"Fisher","year":"2000","journal-title":"Biochemistry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1074\/jbc.M608315200","article-title":"Topology and membrane association of lecithin: Retinol acyltransferase","volume":"282","author":"Moise","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3082","DOI":"10.1021\/acs.biochem.6b00319","article-title":"Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle","volume":"55","author":"Sears","year":"2016","journal-title":"Biochemistry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.bbalip.2008.11.001","article-title":"Hepatic stellate cell lipid droplets: A specialized lipid droplet for retinoid storage","volume":"1791","author":"Blaner","year":"2009","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1002\/hep.30293","article-title":"Hepatic Stellate Cells and Retinoids: Toward A Much More Defined Relationship","volume":"69","author":"Blaner","year":"2019","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0005-2760(96)00041-0","article-title":"Chylomicron assembly and catabolism: Role of apolipoproteins and receptors","volume":"1300","author":"Hussain","year":"1996","journal-title":"Biochim. Biophys. Acta Lipids Lipid Metab."},{"key":"ref_47","first-page":"126","article-title":"The multifaceted nature of retinoid transport and metabolism","volume":"3","author":"Li","year":"2014","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1126\/science.1136244","article-title":"A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A","volume":"315","author":"Kawaguchi","year":"2007","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-386041-5.00001-7","article-title":"The Membrane Receptor for Plasma Retinol-Binding Protein, A New Type of Cell-Surface Receptor","volume":"288","author":"Sun","year":"2011","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Chen, Y., Clarke, O.B., Kim, J., Stowe, S., Kim, Y.K., Assur, Z., Cavalier, M., Godoy-Ruiz, R., Von Alpen, D.C., and Manzini, C. (2016). Structure of the STRA6 receptor for retinol uptake. Science, 353.","DOI":"10.1126\/science.aad8266"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1128\/MCB.00505-12","article-title":"Cross Talk between Signaling and Vitamin A Transport by the Retinol-Binding Protein Receptor STRA6","volume":"32","author":"Berry","year":"2012","journal-title":"Mol. Cell. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.bbalip.2011.04.004","article-title":"Alcohol and aldehyde dehydrogenases: Retinoid metabolic effects in mouse knockout models","volume":"1821","author":"Kumar","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.bbalip.2011.05.004","article-title":"Physiological insights into all-trans-retinoic acid biosynthesis","volume":"1821","author":"Napoli","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"385","DOI":"10.3390\/nu3040385","article-title":"Vitamin A in reproduction and development","volume":"3","author":"Knutson","year":"2011","journal-title":"Nutrients"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.pharmthera.2017.01.004","article-title":"Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases","volume":"173","author":"Napoli","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1093\/jn\/123.suppl_2.362","article-title":"Biosynthesis and metabolism of retinoic acid: Roles of CRBP and CRABP in retinoic acid: Roles of CRBP and CRABP in retinoic acid homeostasis","volume":"123","author":"Napoli","year":"1993","journal-title":"J. Nutr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1517\/17425250903032681","article-title":"The role of CYP26 enzymes in retinoic acid clearance","volume":"5","author":"Thatcher","year":"2009","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev-nutr-072610-145127","article-title":"Cytochrome P450s in the Regulation of Cellular Retinoic Acid Metabolism","volume":"31","author":"Zolfaghari","year":"2011","journal-title":"Annu. Rev. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1096\/fasebj.10.9.8801182","article-title":"Retinoic acid biosynthesis and metabolism","volume":"10","author":"Napoli","year":"1996","journal-title":"FASEB J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1146\/annurev.pharmtox.43.100901.140301","article-title":"Retinoid receptors and their coregulators","volume":"43","author":"Wei","year":"2003","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7158","DOI":"10.1128\/MCB.19.10.7158","article-title":"Physical and functional interactions between cellular retinoic acid binding protein II and the retinoic acid-dependent nuclear complex","volume":"19","author":"Delva","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"23695","DOI":"10.1074\/jbc.274.34.23695","article-title":"Distinct roles for cellular retinoic acid-binding proteins I and II in regulating signaling by retinoic acid","volume":"274","author":"Dong","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1006\/jmbi.2000.4340","article-title":"Localization of the RAR interaction domain of cellular retinoic acid binding protein-II","volume":"305","author":"Budhu","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1194\/jlr.R030833","article-title":"Vitamin A and retinoid signaling: Genomic and nongenomic effects","volume":"54","author":"Piskunov","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_65","first-page":"66","article-title":"Retinoic acid signaling and mouse embryonic stem cell differentiation: Cross talk between genomic and non-genomic effects of RA","volume":"1851","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.bbalip.2011.09.014","article-title":"The retinoid X receptors and their ligands","volume":"1821","author":"Dawson","year":"2012","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.mce.2011.03.025","article-title":"Nuclear retinoic acid receptors: Conductors of the retinoic acid symphony during development","volume":"348","author":"Samarut","year":"2012","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_68","first-page":"163","article-title":"Cellular retinoic acid binding proteins: Genomic and non-genomic functions and their regulation","volume":"81","year":"2016","journal-title":"The Physiology of Vitamin A\u2014Uptake, Transport, Metabolism and Signaling"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1038\/sj.onc.1204329","article-title":"Nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription","volume":"20","author":"Dilworth","year":"2001","journal-title":"Oncogene"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.1210\/en.2017-00353","article-title":"Cellular retinoic acid-binding protein 1 modulates stem cell proliferation to affect learning and memory in male mice","volume":"158","author":"Lin","year":"2017","journal-title":"Endocrinology"},{"key":"ref_71","first-page":"2","article-title":"All trans-retinoic acid analogs promote cancer cell apoptosis through non-genomic Crabp1 mediating ERK1\/2 phosphorylation","volume":"6","author":"Persaud","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1530\/JOE-17-0613","article-title":"CRABP1 protects the heart from isoproterenol-induced acute and chronic remodeling","volume":"236","author":"Park","year":"2018","journal-title":"J. Endocrinol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1042\/bj3610621","article-title":"Retinoic acid activation of the ERK pathway is required for embryonic stem cell commitment into the adipocyte lineage","volume":"361","author":"Bost","year":"2002","journal-title":"Biochem. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1111\/j.1440-169X.2006.00889.x","article-title":"Role of ERK 1\/2 signaling in neuronal differentiation of cultured embryonic stem cells","volume":"48","author":"Li","year":"2006","journal-title":"Dev. Growth Differ."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Park, S.W., Nhieu, J., Persaud, S.D., Miller, M.C., Xia, Y., Lin, Y.W., Lin, Y.L., Kagechika, H., Mayo, K.H., and Wei, L.N. (2019). A new regulatory mechanism for Raf kinase activation, retinoic acid-bound Crabp1. Sci. Rep., in press.","DOI":"10.1038\/s41598-019-47354-7"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1042\/bj3510289","article-title":"Meaningful relationships: The regulation of the Ras\/Raf\/MEK\/ERK pathway by protein interactions","volume":"351","author":"Kolch","year":"2000","journal-title":"Biochem. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S0955-0674(97)80060-9","article-title":"The complexity of Raf-1 regulation","volume":"9","author":"Morrison","year":"1997","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.phrs.2012.04.005","article-title":"ERK1\/2 MAP kinases: Structure, function, and regulation","volume":"66","author":"Roskoski","year":"2012","journal-title":"Pharmacol. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/nrm3979","article-title":"Regulation of RAF protein kinases in ERK signalling","volume":"16","author":"Lavoie","year":"2015","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nsmb1185","article-title":"SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells","volume":"14","author":"Park","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.scr.2012.10.004","article-title":"A short G1 phase is an intrinsic determinant of na\u00efve embryonic stem cell pluripotency","volume":"10","author":"Coronado","year":"2013","journal-title":"Stem Cell Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nrc2347","article-title":"The Cdk inhibitor p27 in human cancer: Prognostic potential and relevance to anticancer therapy","volume":"8","author":"Chu","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.tcb.2011.10.004","article-title":"Multiple degradation pathways regulate versatile CIP\/KIP CDK inhibitors","volume":"22","author":"Starostina","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrg2269","article-title":"Deconstructing stem cell self-renewal: Genetic insights into cell-cycle regulation","volume":"9","author":"Orford","year":"2008","journal-title":"Nat. Rev. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1158\/1078-0432.CCR-10-0752","article-title":"p27: A barometer of signaling deregulation and potential predictor of response to targeted therapies","volume":"17","author":"Wander","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/scrt39","article-title":"Role of Oct4 in maintaining and regaining stem cell pluripotency","volume":"1","author":"Shi","year":"2010","journal-title":"Stem Cell Res. Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"18077","DOI":"10.1074\/jbc.273.29.18077","article-title":"Mechanisms of the mouse orphan nuclear receptor TR2-11-mediated gene suppression","volume":"273","author":"Chinpaisal","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_88","first-page":"405","article-title":"Transcriptional regulation of the Oct4 gene, a master gene for pluripotency","volume":"25","author":"Kellner","year":"2010","journal-title":"Histol. Histopathol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.stem.2009.03.009","article-title":"A Genome-Scale RNAi Screen for Oct4 Modulators Defines a Role of the Paf1 Complex for Embryonic Stem Cell Identity","volume":"4","author":"Ding","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10059-013-2273-1","article-title":"NonO binds to the CpG island of oct4 promoter and functions as a transcriptional activator of oct4 gene expression","volume":"35","author":"Park","year":"2013","journal-title":"Mol. Cells"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/jcb.21244","article-title":"Transcriptional regulation of human Oct4 by steroidogenic factor-1","volume":"101","author":"Yang","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_92","first-page":"1122","article-title":"Characterization of a negative retinoic acid response element in the murine Oct4 promoter","volume":"14","author":"Schoorlemmer","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Park, S.W., Nhieu, J., Lin, Y.W., and Wei, L.N. (2019). All-trans retinoic acid attenuates isoproterenol-induced cardiac dysfunction through Crabp1 to dampen CaMKII activation. Eur. J. Pharmacol., 172485.","DOI":"10.1016\/j.ejphar.2019.172485"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.yjmcc.2011.01.012","article-title":"CaMKII in myocardial hypertrophy and heart failure","volume":"51","author":"Anderson","year":"2011","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1161\/01.CIR.101.14.1634","article-title":"Catecholamines, cardiac \u03b2-adrenergic receptors, and heart failure","volume":"101","author":"Lefkowitz","year":"2000","journal-title":"Circulation"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/1753944714531638","article-title":"Exploration of pharmacological interventions to prevent isoproterenol-induced myocardial infarction in experimental models","volume":"8","author":"Garg","year":"2014","journal-title":"Ther. Adv. Cardiovasc. Dis."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4149\/gpb_2012_015","article-title":"Morphological and functional characteristics of models of experimental myocardial injury induced by isoproterenol","volume":"31","author":"Nichtova","year":"2012","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.cell.2007.02.050","article-title":"Opposing Effects of Retinoic Acid on Cell Growth Result from Alternate Activation of Two Different Nuclear Receptors","volume":"129","author":"Schug","year":"2007","journal-title":"Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3333","DOI":"10.1038\/onc.2011.499","article-title":"A retinoic acid receptor RAR\u03b1 pool present in membrane lipid rafts forms complexes with G protein \u03b1Q to activate p38MAPK","volume":"31","author":"Piskunov","year":"2012","journal-title":"Oncogene"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/emboj.2008.256","article-title":"A coordinated phosphorylation cascade initiated by p38MAPK\/MSK1 directs RAR\u03b1 to target promoters","volume":"28","author":"Bruck","year":"2009","journal-title":"EMBO J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4340","DOI":"10.1073\/pnas.1011115108","article-title":"Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses","volume":"108","author":"Berry","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/15\/3610\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:08:54Z","timestamp":1760188134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/15\/3610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,24]]},"references-count":101,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2019,8]]}},"alternative-id":["ijms20153610"],"URL":"https:\/\/doi.org\/10.3390\/ijms20153610","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,24]]}}}