B4GALT1

What is B4GALT1 Protein?

B4GALT1 gene (beta-1,4-galactosyltransferase 1) is a protein coding gene which situated on the short arm of chromosome 9 at locus 9p21. This gene is unique among the beta4GalT genes because it encodes an enzyme that participates both in glycoconjugate and lactose biosynthesis. For the first activity, the enzyme adds galactose to N-acetylglucosamine residues that are either monosaccharides or the nonreducing ends of glycoprotein carbohydrate chains. The second activity is restricted to lactating mammary tissues where the enzyme forms a heterodimer with alpha-lactalbumin. The two enzymatic forms result from alternate transcription initiation sites and post-translational processing. The B4GALT1 protein is consisted of 398 amino acids and B4GALT1 molecular weight is approximately 43.9 kDa.

What is the Function of B4GALT1 Protein?

The B4GALT1 protein, also known as β1, 4-galactosyltransferase 1, is an enzyme that plays a key role in N-glycan biosynthesis. The function of B4GALT1 is not limited to participating in the glycosylation of glycoproteins, it has also been implicated in a variety of biological processes and diseases, especially in cancer. It was found that high expression of B4GALT1 was associated with increased proliferation and invasion of tumor cells and decreased anti-tumor ability of CD8+ T cells. Mechanistically, B4GALT1 is able to directly mediate N-ligand 1 (PD-L1) glycosylation of programmed death ligand 1 (PD-L1) protein, preventing degradation of PD-L1 at the post-transcriptional level. In addition, B4GALT1 stabilizes TAZ protein by glycosylation and activates transcription of CD274 (the gene for PD-L1), thus promoting immune escape from lung cancer.

B4GALT1 Related Signaling Pathway

B4GALT1 promotes immune escape of lung adenocarcinoma (LUAD) by directly mediating N-linking glycosylation of PD-L1 protein and preventing degradation of PD-L1 at the post-transcriptional level. B4GALT1 and B4GALT5 may be involved in the development of multidrug resistance (MDR) in human leukemia cells by modulating the activity of the hedgehog signaling pathway. The expression of B4GALT1 is associated with cell proliferation and apoptosis in different types of cancer. For example, in breast cancer, the expression of B4GALT1 is regulated by estrogen and affects the proliferation of MCF-7 cells. The expression of B4GALT1 is regulated by several transcription factors, including Ets1 transcription factor and EGF/RAS/ERK signaling pathway.

B4GALT1 Related Diseases

The B4GALT1 protein has been implicated in a variety of diseases, especially cancer. In lung adenocarcinoma, B4GALT1 promotes immune escape of tumor cells by regulating the expression of PD-L1. In leukemia, B4GALT1 is associated with multidrug resistance. In hepatocellular carcinoma, decreased expression of B4GALT1 is associated with tumor aggressiveness and poor prognosis. In addition, abnormal functioning of B4GALT1 has been linked to the development of other types of cancer such as breast cancer and glioma.

Fig1. A schematic diagram illustrating the proposed mechanism by which B4GALT1 regulates HCC invasiveness. (Po-Da Chen, 2023)

Bioapplications of B4GALT1

As a β1, 4-galactosyltransferase, B4GALT1 plays a role in a variety of biological processes, and its related applications are mainly concentrated in the medical field, especially in cancer treatment and drug development. Changes in the activity or expression level of B4GALT1 are closely related to tumor aggressiveness, metastasis, and immune escape ability, making it a potential target for cancer therapy. For example, by inhibiting the activity of B4GALT1 or its expression in tumor cells, it is possible to enhance the sensitivity of tumor cells to immunotherapy, especially in PD-1/PD-L1 immune checkpoint inhibitor therapy. In addition, the role of B4GALT1 in drug resistance also suggests its potential application in the optimization of cancer chemotherapy regimens.

Case Study 1: Yanan Cui, 2023

Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment. Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1). The results showed that B4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. In addition, B4GALT1 stabilized the TAZ protein via glycosylation, which activated CD274 at the transcriptional level.

Fig1. The linear correlations between the H-scores of B4GALT1 and the percentages of CD3, CD8, and H-scores of GAMB.

Fig2. Detection of GST and GST-B4GALT1 proteins.

Case Study 2: Pu Wang, 2020

This study was designed to investigate the role of B4GalT1 in glioblastoma, in vitro and in vivo, to detect whether B4GalT1 knockdown could regulate the development of glioblastoma, and further observe the relationship between B4GalT1 knockdown and the apoptosis and autophagy of glioblastoma. To begin, they looked at TCGA and GEPIA systems to predict the potential function of B4GalT1. Western blot and RT-PCR were used to analyze the expression, or mRNA level, of B4GalT1 at different tissue or cell lines. Next, the occurrence and development of glioblastoma, in vitro and in vivo, was observed by using B4GalT1 knocked down by lentivirus. Finally, the apoptosis and autophagy of glioblastoma was observed in vitro and in vivo. Results show that B4GalT1 was a highly variable gene, and GEPIA and TCGA systems show B4GalT1 expression in GBM tumor tissue was higher than in normal tissue. Pair-wise gene correlation analysis revealed a probable relationship between B4GalT1 and autophagy related proteins. The B4GalT1 expression and mRNA level were increased in tumor cells, or U87 cells. B4GalT1 knocked down by lentivirus could inhibit glioblastoma development, in vitro and in vivo. B4GalT1 knockdown could increase apoptosis and autophagy of glioblastoma in vitro and in vivo.

Fig3. Western blot assay of B4GalT1 expression in SVG-P12, A172, U251 and U87 cells.

Fig4. Survival analysis of Con, sh-B4GalT1 and control-shB4GalT1 mice.

B4GALT1 has several biochemical functions, for example, N-acetyllactosamine synthase activity,UDP-galactosyltransferase activity,alpha-tubulin binding. Some of the functions are cooperated with other proteins, some of the functions could acted by B4GALT1 itself. We selected most functions B4GALT1 had, and list some proteins which have the same functions with B4GALT1. You can find most of the proteins on our site.

B4GALT1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with B4GALT1 here. Most of them are supplied by our site. Hope this information will be useful for your research of B4GALT1.

Dlg4;B4galt1