Abstract
Our ability to overcome the challenges behind metabolic disorders will require a detailed understanding of the regulation of responses to nutrition. The Creb3 transcription factor family appears to have a unique regulatory role that links cellular secretory capacity with development, nutritional state, infection, and other stresses. This role in regulating individual secretory capacity genes could place this family of transcription factors at an important regulatory intersection mediating an animal’s responses to nutrients and other environmental challenges. Interestingly, in both humans and mice, individuals with mutations in Creb3L3/CrebH, one of the Creb3 family members, exhibit hypertriglyceridemia (HTG) thus linking this transcription factor to lipid metabolism. We are beginning to understand how Creb3L3 and related family members are regulated and to dissect the potential redundancy and cross talk between distinct family members, thereby mediating both healthy and pathological responses to the environment. Here, we review the current knowledge on the regulation of Creb3 family transcription factor activity, their target genes, and their role in metabolic disease.
Highlights
The recent rise in obesity and the chronic diseases associated with it are a result of many factors, including increased consumption of sugars and fats
The founding member of the Creb3 family is the Drosophila CrebA protein, which was identified as binding to cyclic-AMP responsive DNA elements (CRE) (Abel et al, 1992; Smolik et al, 1992)
Because of the high identity between the Creb3 family members, their shared function regulating secretory capacity and the overlap in their expression, understanding the potential for the cross talk and redundancy between family members will aid our understanding of the role that these transcription factors play in both healthy and unhealthy responses to nutrition and cellular metabolism
Summary
The recent rise in obesity and the chronic diseases associated with it are a result of many factors, including increased consumption of sugars and fats. The Creb3 family of transcription factors plays an interesting, but not yet fully understood role in regulating the secretory capacity of cells in response to environmental challenges. Because of the high identity between the Creb3 family members, their shared function regulating secretory capacity and the overlap in their expression, understanding the potential for the cross talk and redundancy between family members will aid our understanding of the role that these transcription factors play in both healthy and unhealthy responses to nutrition and cellular metabolism.
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