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Small heterodimer partner-interacting leucine zipper (SMILE) is a member of the cAMP response element-binding protein / activator transcription factor (CREB/ATF) family of basic leucine zipper (bZIP) transcription factors. Structurally, it exists in small and long isoforms resulting from alternative usage of the initiation codon. Though structurally similar to bZIP proteins, SMILE cannot bind to DNA but can homodimerize like them. SMILE acts as a corepressor for nuclear receptors related transcriptional activity and other transcription factors. SMILE plays a crucial role in metabolic signaling pathways by inhibiting DNA binding, competing with coactivators, and directly repressing transcription. This review focuses on the role of SMILE in hepatic glucose and lipid metabolism. Regulation of SMILE improves pathological conditions such as hepatitis, diabetes and fatty liver disease. Therefore, understanding the role of SMILE in metabolism and signaling pathways paves the way to consider SMILE as a potential target in treating liver metabolic diseases.
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Park et al. (2022) studied this question.
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