{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRetinoic acid receptor alpha (RARα) is a ligand‐regulated nuclear transcription factor that in its normal state mediates retinoid‐dependent gene expression programs controlling differentiation and proliferation. In the hematopoietic system, its deregulation—most notably via formation of fusion proteins such as PML–RARα and STAT5b–RARα—is a critical driver of acute promyelocytic leukemia (APL). These chimeric proteins act as dominant repressors by altering chromatin structure and silencing key differentiation genes; treatment with all‐trans retinoic acid (ATRA) and arsenic trioxide can trigger their degradation and restore maturation. In addition, RARα dysfunction can be compounded by cooperating genetic lesions and epigenetic modifications that further block differentiation and promote leukemogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond hematologic malignancies, RARα plays an important role in solid tumors such as breast cancer. In estrogen receptor–positive cancer cells, RARα not only contributes to the classical retinoid transcriptional program but also collaborates with estrogen receptor signaling. Its expression can be induced via intronic regulatory elements and is required for optimal estrogen‐dependent transcription and growth inhibition, underscoring its role in modulating cell proliferation in hormone‐responsive tumors."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its well‐established genomic functions, rapid non‐genomic actions of RARα have been documented. Ligand engagement can prompt RARα to associate with components of extra‐nuclear signaling complexes—for example, its interaction with phosphatidylinositol 3-kinase and G protein subunits at membrane lipid rafts facilitates activation of kinase cascades (including p38 MAPK). Moreover, cAMP‐dependent phosphorylation events modulate RARα function and enhance its DNA binding, linking second messenger signaling to retinoid responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRARα activity is finely tuned by a host of coregulators and post‐translational modifications. Coactivators such as ASXL1 (which cooperates with SRC-1) enhance RARα transcriptional activity, whereas corepressors and structural rearrangements in the receptor underpin its basal repressive state in the absence of ligand. The recruitment of factors such as TopoIIβ further modulates its function, delineating complex regulatory networks that are vital in both normal physiology and in the aberrant transcriptional repression observed with fusion oncoproteins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "24", "end_ref": "27"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther studies have implicated RARα in diverse disease contexts. In neurodegenerative settings, microRNAs such as miR-138 target RARα, thereby modulating kinase pathways (eg, GSK-3β) and contributing to tau hyperphosphorylation. In viral infections, RARα regulates the expression of host cell receptors such as NTCP, impacting hepatitis B virus entry. Moreover, aberrant RARα expression has been linked to cancer stem cell features in multiple myeloma, while viral proteins (eg, from hepatitis C) can modulate its transcriptional activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "28", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations and structural alterations affecting RARα, including those present in fusion oncoproteins, underlie resistance to differentiation therapies such as ATRA and arsenic trioxide. Specific point mutations and alterations in the recruitment of corepressors (or shifts in coactivator interactions) can hamper ligand-induced degradation of the oncoprotein, thereby contributing to therapeutic resistance. Such molecular insights are crucial for understanding variable responses in diseases like APL and for developing strategies to overcome retinoid resistance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, recent work has highlighted additional roles for RARα in the regulation of noncoding elements. For example, its activation of specific DR2 Alu repeats in embryonic stem cells underscores a mechanism by which RARα influences the decay of stem cell mRNAs and fosters differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "L Z He, M Bhaumik, C Tribioli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two critical hits for promyelocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1097-2765(00)00111-8"}], "href": "https://doi.org/10.1016/s1097-2765(00"}, {"type": "t", "text": "00111-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11106752"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11106752"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.122233699"}], "href": "https://doi.org/10.1073/pnas.122233699"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12060771"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12060771"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Matthew J Walter, John S Park, Rhonda E Ries, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced PU.1 expression causes myeloid progenitor expansion and increased leukemia penetrance in mice expressing PML-RARalpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0504247102"}], "href": "https://doi.org/10.1073/pnas.0504247102"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16113082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16113082"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Francesco Fazi, Giuseppe Zardo, Vania Gelmetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heterochromatic gene repression of the retinoic acid pathway in acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2006-09-045781"}], "href": "https://doi.org/10.1182/blood-2006-09-045781"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17244680"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17244680"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Claudia Hoemme, Abdul Peerzada, Gerhard Behre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chromatin modifications induced by PML-RARalpha repress critical targets in leukemogenesis as analyzed by ChIP-Chip."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-03-079921"}], "href": "https://doi.org/10.1182/blood-2007-03-079921"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18024792"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18024792"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rihab Nasr, Marie-Claude Guillemin, Omar Ferhi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PML-RARalpha initiates leukemia by conferring properties of self-renewal to committed promyelocytic progenitors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2009.63"}], "href": "https://doi.org/10.1038/leu.2009.63"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19322209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19322209"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Joost H A Martens, Arie B Brinkman, Femke Simmer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PML-RARalpha/RXR Alters the Epigenetic Landscape in Acute Promyelocytic Leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2009.12.042"}], "href": "https://doi.org/10.1016/j.ccr.2009.12.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20159609"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20159609"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Pauline Isakson, Magnar Bjørås, Stig Ove Bøe, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "BCOR as a novel fusion partner of retinoic acid receptor alpha in a t(X;17)(p11;q12) variant of acute promyelocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-01-264432"}], "href": "https://doi.org/10.1182/blood-2010-01-264432"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20807888"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20807888"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Roberta Carbone, Oronza A Botrugno, Simona Ronzoni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recruitment of the histone methyltransferase SUV39H1 and its role in the oncogenic properties of the leukemia-associated PML-retinoic acid receptor fusion protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.4.1288-1296.2006"}], "href": "https://doi.org/10.1128/MCB.26.4.1288-1296.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16449642"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16449642"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Maaike Luesink, Jeroen L A Pennings, Willemijn M Wissink, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-02-204834"}], "href": "https://doi.org/10.1182/blood-2009-02-204834"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19828696"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19828696"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Paul A O'Connell, Patricia A Madureira, Jason N Berman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of S100A10 by the PML-RAR-α oncoprotein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-07-298851"}], "href": "https://doi.org/10.1182/blood-2010-07-298851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21310922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21310922"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Fabien Guidez, Sarah Parks, Henna Wong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RARalpha-PLZF overcomes PLZF-mediated repression of CRABPI, contributing to retinoid resistance in t(11;17) acute promyelocytic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0704433104"}], "href": "https://doi.org/10.1073/pnas.0704433104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18000064"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18000064"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Caryn S Ross-Innes, Rory Stark, Kelly A Holmes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.552910"}], "href": "https://doi.org/10.1101/gad.552910"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20080953"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20080953"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Sujun Hua, Ralf Kittler, Kevin P White "}, {"type": "b", "children": [{"type": "t", "text": "Genomic antagonism between retinoic acid and estrogen signaling in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2009.04.043"}], "href": "https://doi.org/10.1016/j.cell.2009.04.043"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19563758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19563758"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Josée Laganière, Geneviève Deblois, Vincent Giguère "}, {"type": "b", "children": [{"type": "t", "text": "Functional genomics identifies a mechanism for estrogen activation of the retinoic acid receptor alpha1 gene in breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2005-0040"}], "href": "https://doi.org/10.1210/me.2005-0040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15831516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15831516"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Min Lu, Rafael Mira-y-Lopez, Shigeo Nakajo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of estrogen receptor alpha, retinoic acid receptor alpha and cellular retinoic acid binding protein II genes is coordinately regulated in human breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1208661"}], "href": "https://doi.org/10.1038/sj.onc.1208661"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15870697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15870697"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Susana Masiá, Susana Alvarez, Angel R de Lera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rapid, nongenomic actions of retinoic acid on phosphatidylinositol-3-kinase signaling pathway mediated by the retinoic acid receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Endocrinol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/me.2007-0062"}], "href": "https://doi.org/10.1210/me.2007-0062"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17595318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17595318"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Emilie Gaillard, Nathalie Bruck, Yann Brelivet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phosphorylation by PKA potentiates retinoic acid receptor alpha activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0509717103"}], "href": "https://doi.org/10.1073/pnas.0509717103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16769902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16769902"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "A Piskunov, C Rochette-Egly "}, {"type": "b", "children": [{"type": "t", "text": "A retinoic acid receptor RARα pool present in membrane lipid rafts forms complexes with G protein αQ to activate p38MAPK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.499"}], "href": "https://doi.org/10.1038/onc.2011.499"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22056876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22056876"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Yang-Sook Cho, Eun-Joo Kim, Ui-Hyun Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Additional sex comb-like 1 (ASXL1), in cooperation with SRC-1, acts as a ligand-dependent coactivator for retinoic acid receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M512616200"}], "href": "https://doi.org/10.1074/jbc.M512616200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16606617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16606617"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Albane le Maire, Catherine Teyssier, Cathie Erb, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A unique secondary-structure switch controls constitutive gene repression by retinoic acid receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1855"}], "href": "https://doi.org/10.1038/nsmb.1855"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20543827"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20543827"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Raffaella Villa, Lluis Morey, Veronica A Raker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The methyl-CpG binding protein MBD1 is required for PML-RARalpha function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0509343103"}], "href": "https://doi.org/10.1073/pnas.0509343103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16432238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16432238"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Suzan McNamara, Hongling Wang, Nessrine Hanna, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Topoisomerase IIbeta negatively modulates retinoic acid receptor alpha function: a novel mechanism of retinoic acid resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01576-07"}], "href": "https://doi.org/10.1128/MCB.01576-07"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18212063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18212063"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Xiong Wang, Lu Tan, Yanjun Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-138 promotes tau phosphorylation by targeting retinoic acid receptor alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2015.02.001"}], "href": "https://doi.org/10.1016/j.febslet.2015.02.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25680531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25680531"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Inna G Ovsyannikova, Neelam Dhiman, Iana H Haralambieva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-009-0763-1"}], "href": "https://doi.org/10.1007/s00439-009-0763-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19902255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19902255"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Koichi Watashi, Makoto Hijikata, Ayako Tagawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Modulation of retinoid signaling by a cytoplasmic viral protein via sequestration of Sp110b, a potent transcriptional corepressor of retinoic acid receptor, from the nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.21.7498-7509.2003"}], "href": "https://doi.org/10.1128/MCB.23.21.7498-7509.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14559998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14559998"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Senko Tsukuda, Koichi Watashi, Masashi Iwamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dysregulation of retinoic acid receptor diminishes hepatocyte permissiveness to hepatitis B virus infection through modulation of sodium taurocholate cotransporting polypeptide (NTCP) expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.602540"}], "href": "https://doi.org/10.1074/jbc.M114.602540"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25550158"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25550158"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Henrik J Johansson, Betzabe C Sanchez, Filip Mundt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Retinoic acid receptor alpha is associated with tamoxifen resistance in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms3175"}], "href": "https://doi.org/10.1038/ncomms3175"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23868472"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23868472"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Krishna K Ratnam, Xiaobei Feng, Peter Y Chuang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of the retinoic acid receptor-α in HIV-associated nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ki.2010.470"}], "href": "https://doi.org/10.1038/ki.2010.470"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21150871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21150871"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Emi Goto, Akihiro Tomita, Fumihiko Hayakawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Missense mutations in PML-RARA are critical for the lack of responsiveness to arsenic trioxide treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-01-329433"}], "href": "https://doi.org/10.1182/blood-2011-01-329433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21613260"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21613260"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Takemi Tanaka, Kwang S Suh, Angela M Lo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "p21WAF1/CIP1 is a common transcriptional target of retinoid receptors: pleiotropic regulatory mechanism through retinoic acid receptor (RAR)/retinoid X receptor (RXR) heterodimer and RXR/RXR homodimer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M701700200"}], "href": "https://doi.org/10.1074/jbc.M701700200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17656367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17656367"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Harry D Dawson, Gary Collins, Robert Pyle, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Retinoic Acid Receptor-alpha mediates human T-cell activation and Th2 cytokine and chemokine production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2172-9-16"}], "href": "https://doi.org/10.1186/1471-2172-9-16"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18416830"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18416830"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Tonia C Carter, Anne M Molloy, Faith Pangilinan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Testing reported associations of genetic risk factors for oral clefts in a large Irish study population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Birth Defects Res A Clin Mol Teratol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bdra.20639"}], "href": "https://doi.org/10.1002/bdra.20639"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19937600"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19937600"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "QiDong Hu, Bogdan Tanasa, Michele Trabucchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.2400"}], "href": "https://doi.org/10.1038/nsmb.2400"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23064648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23064648"}]}]}]}