B4GALT1

Official Full Name

beta-1,4-galactosyltransferase 1

Organism

Homo sapiens

GeneID

2683

Background

This gene is one of seven beta-1,4-galactosyltransferase (beta4GalT) genes. They encode type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a beta1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: beta4GalT1 and beta4GalT2, beta4GalT3 and beta4GalT4, beta4GalT5 and beta4GalT6, and beta4GalT7. 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 to catalyze UDP-galactose + D-glucose <=> UDP + lactose. The two enzymatic forms result from alternate transcription initiation sites and post-translational processing. Two transcripts, which differ only at the 5' end, with approximate lengths of 4.1 kb and 3.9 kb encode the same protein. The longer transcript encodes the type II membrane-bound, trans-Golgi resident protein involved in glycoconjugate biosynthesis. The shorter transcript encodes a protein which is cleaved to form the soluble lactose synthase. [provided by RefSeq, Jul 2008]

Synonyms

GT1; GTB; CDG2D; GGTB2; CLDLFIB; B4GAL-T1; beta4Gal-T1;

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Detailed Information

Recent Research Progress

The β4-galactosyltransferase (B4GALT) family has seven members and each of those members possesses distinct biological functions on account of different receptor specificity, tissue distribution, and temporal expression. B4GALT1 binds galactose to the N-acetylglucosamine outer arm in the N-linked oligosaccharide of IgG, and the B4GALT1 level is continuously linked to the continuation of the terminal galactose in IgG, which is associated with an adaptive immune response. The importance of glycan β4-galactosylation of glycans is well known, and the galactosylation can be part of many biological activities, such as cancer progression. Changes in expression of B4GALT1 have been documented in certain types of cancer, such as breast cancer, colon cancer, hepatocellular cancer, lung cancer, leukemia, neuroblastoma and prostate cancer, and are connected to cancer cell proliferation, invasion, metastasis and Resistance drug.

B4GALT1 and MIBC

The fourth most commonly diagnosed cancer, bladder cancer has an occurrence rate of about 7%, is the eighth most common cause of male death (about 4%). Recent studies have shown that B4GALT1 expression was not associated with clinical prognostic markers, but it was connected to overall survival (OS). In addition, high levels of B4GALT1 expression were independent indicators of poor OS. Inclusion of B4GALT1 in the prognostic model showed higher prediction accuracy than the primary model. Moreover, there was a positive Pearson correlation between B4GALT1 expression and inhibitory receptor ligand expression, such as programmed death-ligand 1 (PD-L1) and Cytotoxic T-lymphocyte-associated protein 4 (CTLA4). Most significantly, the advantage of adjuvant chemotherapy (ACT) noted in patients with low B4GALT1 expression in pT3/4 or N⁺ bladder cancer was greater than in patients with high B4GALT1 expression. In conclusion, B4GALT1 may be a prognostic factor for muscle invasive bladder cancer (MIBC), which may be a predictive marker for ACT in patients with pT3 / 4 or N⁺. The high expression of B4GALT1 can lead to a more effective immunosuppressive microenvironment, which helps to better select the combination of chemotherapy and immunotherapy in patients with MIBC.

B4GALT1 and CML

Abnormal expression of suppressor of cytokine signaling 3 (SOCS3) is associated with myeloproliferative neoplasms and SOCS3 plays an important role in the pathogenesis of chronic myeloid leukemia (CML). Recent studies have shown that miR-124-3p was obviously up-regulated by SOCS3 overexpression. In turn, changes in the expression level of miR-124-3p affected the effect of SOCS3 on CML cells. Furthermore, B4GALT1 is a multidrug resistance gene that is a target gene for the SOCS3 / miR-124-3p axis. These findings demonstrated the existence of molecular networks involved in the dysregulation of SOCS3, miR-124-3p and B4GALT1, which may provide new insights into tumor biology and present a useful target for therapeutic interference of CML under certain circumstances.

B4GALT1 and ccRCC

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and its incidence increases by 2.5% per year worldwide. A recent association between high expression of B4GALT1 and increased risk of death in patients with non-metastatic ccRCC after surgery has been reported. High B4GALT1 expression was positively correlated with histological necrosis, tumor T stage, and Fuhrman grading, which strongly suggested that B4GALT1 plays a key role in ccRCC development and progression. What’s more, the accuracy of the UISS (University of California Integrated Staging System) and SSIGN (Mayo Clinic stage, size, grade and necrosis score) prognostic models was improved when B4GALT1 expression was added. In summary, the current study identified B4GALT1 expression as a potential independent adverse prognostic indicator for OS in patients with non-metastatic ccRCC.

In conclusion, B4GALT1 expression plays an important role in the pathogenesis of various cancers. Combining B4GALT1 expression with a conventional prognostic model can improve the prognosis accuracy. Further research may attempt to verify whether B4GALT1 can be used as a new therapeutic target.

References:

Huyang Xie, et al. B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscleinvasive bladder cancer patients. BMC Cancer, 2018, 18:590
Yu-xiao Liu, et al. MiR-124-3p/B4GALT1 axis plays an important role in SOCS3-regulated growth and chemo-sensitivity of CML. Journal of Hematology & Oncology, 2016, 9:69
Jie Wu, et al. ZFX modulates the growth of human leukemic cells via B4GALT1. Acta Biochim Biophys Sin, 2016, 48(12): 1120–1127
AL-OBAIDE, et al. Multifaceted roles of 5'-regulatory region of the cancer associated gene B4GALT1 and its comparison with the gene family. International Journal Of Oncology, 2015,47: 1393-1404,
Huyang Xie, et al. Increased B4GALT1 expression associates with adverse outcome in patients with non-metastatic clear cell renal cell carcinoma. Oncotarget, 2016, 7:22

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