Emerging Role of SMILE in Liver Metabolism
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 homodime...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2907 |
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| author | Nanthini Sadasivam Kamalakannan Radhakrishnan Hueng-Sik Choi Don-Kyu Kim |
| author_facet | Nanthini Sadasivam Kamalakannan Radhakrishnan Hueng-Sik Choi Don-Kyu Kim |
| author_sort | Nanthini Sadasivam |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T09:39:57Z |
| format | Article |
| id | doaj.art-755d46e7f5c645a195536a7f76aa83af |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:39:57Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-755d46e7f5c645a195536a7f76aa83af2023-11-16T17:04:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243290710.3390/ijms24032907Emerging Role of SMILE in Liver MetabolismNanthini Sadasivam0Kamalakannan Radhakrishnan1Hueng-Sik Choi2Don-Kyu Kim3Department of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, Republic of KoreaClinical Vaccine R&D Centre, Department of Microbiology, Combinatorial Tumour Immunotheraphy MRC, Medical School, Chonnam National University, Gwangju 58128, Republic of KoreaSchool of Biological Sciences and Technology, Chonnam National University, Gwangju 61186, Republic of KoreaDepartment of Integrative Food, Bioscience and Biotechnology, Chonnam National University, Gwangju 61186, Republic of KoreaSmall 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.https://www.mdpi.com/1422-0067/24/3/2907SMILEtranscription factorsnuclear receptorsCREBZFbZIP proteinsliver |
| spellingShingle | Nanthini Sadasivam Kamalakannan Radhakrishnan Hueng-Sik Choi Don-Kyu Kim Emerging Role of SMILE in Liver Metabolism International Journal of Molecular Sciences SMILE transcription factors nuclear receptors CREBZF bZIP proteins liver |
| title | Emerging Role of SMILE in Liver Metabolism |
| title_full | Emerging Role of SMILE in Liver Metabolism |
| title_fullStr | Emerging Role of SMILE in Liver Metabolism |
| title_full_unstemmed | Emerging Role of SMILE in Liver Metabolism |
| title_short | Emerging Role of SMILE in Liver Metabolism |
| title_sort | emerging role of smile in liver metabolism |
| topic | SMILE transcription factors nuclear receptors CREBZF bZIP proteins liver |
| url | https://www.mdpi.com/1422-0067/24/3/2907 |
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