Controlling Diabetes: The Transcription Factor ATF/CREB Protein Family

On February 20, 2021, researcher Yu Li of the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences published a review paper entitled: Regulation of hepatic metabolism and cell growth by the ATF/CREB family of transcription factor online in Diabetes.

The review article systematically summarizes the research results of the ATF/CREB family of transcription factors in hepatic glucose and lipid metabolism, cell growth and tumor, and provides an outlook on the potential clinical applications and future research directions of this family.

The liver plays a crucial role in the homeostatic regulation of human metabolism. Imbalance of glucose and fat metabolism in the liver can easily lead to metabolic diseases such as insulin resistance, type 2 diabetes, and non-alcoholic fatty liver disease, as well as increase the risk of several cancers, such as hepatocellular carcinoma. Various transcription factors or cofactor-mediated signaling pathways play a very important role in the development of these diseases.

The ATF/CREB family is a conserved family of proteins that all contain a segment of the basic leucine zipper structural domain and play important transcriptional regulatory functions. Currently, more than 20 proteins have been named with the ATF/CREB family prefix. These protein members can regulate the expression of downstream genes by forming homo- or heterodimers.

More interestingly, this protein family can also influence the ability of cells to respond to different external stimuli by altering their transcriptional activity through sensing extracellular signals such as nutrients, energy status, and hormone levels, thus exerting their function in regulating systemic homeostasis in a variety of important tissues and organs, especially the liver.

Currently, much attention is paid to how nutrient overload under physiological and pathological conditions disrupts hepatocyte homeostasis and leads to disturbances in glucolipid metabolism, hepatic fat accumulation and reduced insulin sensitivity, ultimately leading to the development of nonalcoholic fatty liver disease and even hepatocellular carcinoma.

This review paper takes the ATF/CREB family as an entry point, summarizes the definition of the family members and the subfamilies they belong to, and discusses their roles in the liver as a bridge between extracellular nutrient signaling, growth factor sensing and glycolipid metabolism, and maintenance of cell proliferation homeostasis, and discusses the molecular regulatory mechanisms of the ATF/CREB protein family under physiological and pathological conditions.