{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:05:53Z","timestamp":1788887153481,"version":"build-2803163510"},"reference-count":84,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["2021R1A2C1011136"],"award-info":[{"award-number":["2021R1A2C1011136"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["NRF-2021R1A2C3004923"],"award-info":[{"award-number":["NRF-2021R1A2C3004923"]}]},{"name":"National Research Foundation of Korea (NRF)","award":["2020-3915"],"award-info":[{"award-number":["2020-3915"]}]},{"name":"Chonnam National University","award":["2021R1A2C1011136"],"award-info":[{"award-number":["2021R1A2C1011136"]}]},{"name":"Chonnam National University","award":["NRF-2021R1A2C3004923"],"award-info":[{"award-number":["NRF-2021R1A2C3004923"]}]},{"name":"Chonnam National University","award":["2020-3915"],"award-info":[{"award-number":["2020-3915"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Small heterodimer partner-interacting leucine zipper (SMILE) is a member of the CREB\/ATF family of basic leucine zipper (bZIP) transcription factors. SMILE has two isoforms, a small and long isoform, resulting from alternative usage of the initiation codon. Interestingly, although SMILE can homodimerize similar to other bZIP proteins, it cannot bind to DNA. As a result, SMILE acts as a co-repressor in nuclear receptor signaling and other transcription factors through its DNA binding inhibition, coactivator competition, and direct repression, thereby regulating the expression of target genes. Therefore, the knockdown of SMILE increases the transactivation of transcription factors. Recent findings suggest that SMILE is an important regulator of metabolic signals and pathways by causing changes in glucose, lipid, and iron metabolism in the liver. The regulation of SMILE plays an important role in pathological conditions such as hepatitis, diabetes, fatty liver disease, and controlling the energy metabolism in the liver. This review focuses on the role of SMILE and its repressive actions on the transcriptional activity of nuclear receptors and bZIP transcription factors and its effects on liver metabolism. Understanding the importance of SMILE in liver metabolism and signaling pathways paves the way to utilize SMILE as a target in treating liver diseases.<\/jats:p>","DOI":"10.3390\/ijms24032907","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T02:35:10Z","timestamp":1675391710000},"page":"2907","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Emerging Role of SMILE in Liver Metabolism"],"prefix":"10.3390","volume":"24","author":[{"given":"Nanthini","family":"Sadasivam","sequence":"first","affiliation":[{"name":"Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0890-8692","authenticated-orcid":false,"given":"Kamalakannan","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Clinical Vaccine R&D Centre, Department of Microbiology, Combinatorial Tumour Immunotheraphy MRC, Medical School, Chonnam National University, Gwangju 58128, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hueng-Sik","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6251-6438","authenticated-orcid":false,"given":"Don-Kyu","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1093\/nar\/28.12.2446","article-title":"Zhangfei: A second cellular protein interacts with herpes simplex virus accessory factor HCF in a manner similar to Luman and VP16","volume":"28","author":"Lu","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1016\/j.bbrc.2005.11.139","article-title":"Identification and characterization of the DNA-binding properties of a Zhangfei homologue in Japanese pufferfish, Takifugu rubripes","volume":"339","author":"Cockram","year":"2006","journal-title":"Biochem. 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