Figure 3.

Transcriptional regulation of target genes by XBP1s. XBP1s regulates the transcription of various target genes that constitute unique subsets depending on the specific stimuli and cell types. In many studies, XBP1s has been shown to regulate genes that are involved in various cellular processes, such as the ER stress response, protein secretion, lipid and glucose metabolism, immune responses, and cancer development. XBP1s was initially known to play an important role in the development and maintenance of highly secretory cells, such as plasma cells, pancreatic acinar cells and β-cells, hepatocytes, and intestinal Paneth cells. (A) Moreover, XBP1s is a crucial transcription factor for lipid metabolisms involved in the biosynthesis of ER membrane, hepatic lipogenesis, and adipocyte differentiation. (B) XBP1s plays an important role in glucose metabolism by regulating the transcription of UPR- and non-UPR-associated genes in hepatocytes, pancreatic cells, and adipocytes. (C) Several studies have reported that XBP1s regulates the development, differentiation, and immune responses of various immune cells, such as B cells, T cells, macrophages, and dendritic cells. (D) In addition, XBP1s is a crucial regulator of tumorigenesis by regulating the transcription of tumor cell-related genes. XBP1s regulates the development, progression, and metastasis of various tumors, such as triple-negative breast cancer (TNBC), melanoma, hepatocellular carcinoma (HCC), ER-positive breast cancer, and colorectal cancer. (E) Alpha-1 antitrypsin (AAT) is mainly produced by hepatocytes, whereas Z variant of AAT (ZAAT) induces the accumulation of misfolded AAT, leading to AAT deficiency. The function and target genes of XBP1s in AATD have not been well elucidated. (F) XBP1s plays an important role in neurodegenerative disorders and brain function.