{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Activating transcription factor 1 (ATF1) is a member of the CREB/ATF family of transcription factors that plays multifaceted roles in cellular homeostasis and stress responses by regulating gene expression in a context‐dependent manner. In macrophages, for example, phosphorylated ATF1 is induced by heme and, in turn, co‐induces heme oxygenase‐1 (HO‐1) and liver X receptor–β, thereby promoting an adaptive, anti–foam cell phenotype in response to intraplaque hemorrhage (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the setting of oncogenesis, a chimeric fusion between EWSR1 and ATF1 drives aberrant transcriptional programs in clear cell sarcoma by occupying promoters such as that of MITF, which is critical for melanocytic differentiation and tumor survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Furthermore, ATF1 is targeted and activated by several kinases—including CDK3, AMPK, MSK, and HIPK2—that phosphorylate specific residues and thereby modulate its transcriptional activity in cell proliferation, stress response, and survival pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its activity is also tightly controlled by protein–protein interactions; for instance, PIAS3 antagonizes an ATF1-mediated repression of the ferritin H antioxidant gene by interfering with its binding to the antioxidant-responsive element."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Post-transcriptional mechanisms contribute as well, with microRNAs such as miR-34c and miR-30a directly targeting ATF1 to influence cell survival processes in germ cells and to modulate radiosensitivity in non–small cell lung cancer, respectively."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In the immune compartment, ATF1 participates in transcriptional regulation by cooperating with other factors—such as NLRC5 and components of the enhanceosome—to support MHC class I gene expression, and it binds to cAMP responsive elements in B-cell promoters to drive immune gene activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, in nasopharyngeal carcinoma, prolyl isomerase Pin1 interacts with ATF1 at Thr184 to enhance its stability and transcriptional activity, thereby promoting oncogenic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these studies underscore that ATF1 is a highly regulated transcription factor whose phosphorylation state, interacting partners, and posttranscriptional control mechanisms critically determine whether it acts as a transcriptional activator or repressor, with important implications for inflammation, oncogenesis, immune regulation, and therapeutic responsiveness.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joseph J Boyle, Michael Johns, Theresa Kampfer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activating transcription factor 1 directs Mhem atheroprotective macrophages through coordinated iron handling and foam cell protection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.111.247577"}], "href": "https://doi.org/10.1161/CIRCRESAHA.111.247577"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22052915"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22052915"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ian J Davis, Jessica J Kim, Fatih Ozsolak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic MITF dysregulation in clear cell sarcoma: defining the MiT family of human cancers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccr.2006.04.021"}], "href": "https://doi.org/10.1016/j.ccr.2006.04.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16766266"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16766266"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Duo Zheng, Yong-Yeon Cho, Andy T Y Lau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-08-1137"}], "href": "https://doi.org/10.1158/0008-5472.CAN-08-1137"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18794154"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18794154"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kiros Hailemariam, Kenta Iwasaki, Bo-Wen Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.073627"}], "href": "https://doi.org/10.1242/jcs.073627"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20980392"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20980392"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Kenta Iwasaki, Kiros Hailemariam, Yoshiaki Tsuji "}, {"type": "b", "children": [{"type": "t", "text": "PIAS3 interacts with ATF1 and regulates the human ferritin H gene through an antioxidant-responsive element."}]}, {"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.M701477200"}], "href": "https://doi.org/10.1074/jbc.M701477200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17565989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17565989"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xiaoxuan Liang, Doudou Zhou, Chao Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA-34c enhances murine male germ cell apoptosis through targeting ATF1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0033861"}], "href": "https://doi.org/10.1371/journal.pone.0033861"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22479460"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22479460"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yuyan Guo, Wenze Sun, Tuotuo Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2017.5448"}], "href": "https://doi.org/10.3892/or.2017.5448"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28259977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28259977"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Torsten B Meissner, Yuen-Joyce Liu, Kyoung-Hee Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NLRC5 cooperates with the RFX transcription factor complex to induce MHC class I gene expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1103160"}], "href": "https://doi.org/10.4049/jimmunol.1103160"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22490869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22490869"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Nienke van der Stoep, Edwin Quinten, Peter J van den Elsen "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of the MHC class II trans-activator (CIITA) promoter III: identification of a novel regulatory region in the 5'-untranslated region and an important role for cAMP-responsive element binding protein 1 and activating transcription factor-1 in CIITA-promoter III transcriptional activation in B lymphocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.169.9.5061"}], "href": "https://doi.org/10.4049/jimmunol.169.9.5061"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12391222"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12391222"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Guo-Liang Huang, Dan Liao, Hua Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase Pin1 in nasopharyngeal carcinoma progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2016.349"}], "href": "https://doi.org/10.1038/cddis.2016.349"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28032861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28032861"}]}]}]}