Importance of N-Glycosylation on CD147 for  Its Biological Functions

Bai, Yang; Huang, Wan; Ma, Li-Tian; Jiang, Jian‐Li; Chen, Zhi‐Nan

doi:10.3390/ijms15046356

Cited by 95 publications

(106 citation statements)

References 120 publications

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“…Three glycosylation sites have been identified within its Ig-like domains and are postulated to serve as a regulatory mechanism of CD147 function (78). Moreover, the nature of oligosaccharides and HG/LG ratio has been shown to affect many diverse physiologic processes central to CD147 from tumor invasion to embryo implantation (79). Our studies show that VH4-34-encoded IgM Abs bound only a particular glycan moiety on CD147; such reagents that distinguish CD147 based on its glycosylation flavor may be useful in unraveling the central role of CD147 in many cellular processes.…”

Section: Discussionmentioning

confidence: 99%

“…Although the CD147-CD98 complex is ubiquitous, SC-PNAL expression on this complex is specific to B lymphocytes, B cell malignancies, and certain epithelial cancers. Expression of SC-PNAL on epithelial cancers varies from high to low and may be a cross-reactive epitope emerging from the aberrant glycosylation linked to malignant transformation (79,80). Nontemplate-based glycosylation is a coordinated, controlled process that leads to many complex glycan products.…”

Section: Discussionmentioning

confidence: 99%

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Identification of Cell Surface Straight Chain Poly-N-Acetyl-Lactosamine Bearing Protein Ligands for VH4-34–Encoded Natural IgM Antibodies

Bhat

Adams

Chen

et al. 2015

The Journal of Immunology

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B cell binding and cytotoxicity by human VH4-34–encoded Abs of the IgM isotype has been well documented. A VH4-34-IgM has recently shown a favorable early response in a phase 1 trial for treatment of B cell acute lymphoblastic leukemia. Although its B cell ligand has been identified as straight chain poly-N-acetyl-lactosamine (SC-PNAL), the carrier of the sugar moiety has not been identified. Using nanoelectrospray ionization mass spectrometry, we identify the metabolic activation related protein complex of CD147-CD98 as a major carrier of poly-N-acetyl-lactosamine (SC-PNAL) on human pre-B cell line Nalm-6. Previous studies have suggested CD45 as the SC-PNAL carrier for VH4-34–encoded IgG Abs. Because Nalm-6 is CD45 negative, human peripheral blood B lymphocytes and human B cell line, Reh, with high CD45 expression, were examined for SC-PNAL carrier proteins. Western blot analysis shows that the CD147-98 complex is indeed immunoprecipitated by VH4-34–encoded IgMs from human peripheral blood B lymphocytes and human B cell lines, Reh, OCI-Ly8, and Nalm-6. However, CD45 is immunoprecipitated only from peripheral B lymphocytes, but not from Reh despite the high expression of CD45. These results suggest that human B cells retain SC-PNAL on the CD147-98 complex, but modulate the sugar moiety on CD45. Because the carbohydrate moiety may act as a selecting Ag for VH4-34 autoantibody repertoire, its differential expression on proteins may provide a clue to the intricate atypical regulation of the VH4-34 gene.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of Cell Surface Straight Chain Poly-N-Acetyl-Lactosamine Bearing Protein Ligands for VH4-34–Encoded Natural IgM Antibodies

Bhat

Adams

Chen

et al. 2015

The Journal of Immunology

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“…3.3. Tumor-associated antigen (CD147) CD147, a tumor-associated antigen, is a transmembrane protein and a member of the immunoglobulin receptor family and is highly expressed on the cell surface of various tumor cells (Bai et al, 2014). The role of CD147 in tumorigenesis is related to the inducement of MMP expression.…”

Section: Adhesion and Signal Moleculesmentioning

confidence: 99%

Glycosylation changes leading to the increase in size on the common core of N-glycans, required enzymes, and related cancer-associated proteins

Karaçalı¹,

İzzetoğlu²,

Deveci³

2014

Turk J Biol

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Glycan parts of glycoconjugates on the surfaces of cells regulate many kinds of interactions between the cells and their immediate environments. Alterations in glycosylation on the cancer-associated glycoproteins are responsible for changes in their molecular interactions and biological functions. Glycosylation changes occur in the core and/or at the nonreducing end of the oligosaccharide chains of N-glycans. In this review, we focus on the branching of the common core structure of N-glycans, the responsible enzyme, and the extensions of some of the branches causing size increases on the surface of tumor cells. Abnormal branching, elongation of the branches, and increasing size of the common core of N-glycans are the typical features of these changes and are related with malignant transformations. Seven N-acetylglucosaminyltransferases (GnTs) (GnT-I, GnT-II, GnT-III, GnT-IV, GnT-V, GnT-VI, and GnT-IX) and α1,6-fucosyltransferase (FUT8) initiate the new branches on the core. GnT-IV, GnT-V, and GnT-IX initiate the branches available for poly-LacNAc extensions, which are responsible for tumor progression and metastasis. GnT-III prevents the catalytic activity of GnT-II, GnT-IV, GnT-V, and FUT8 to form branching and elongation of the branches. The contributions of GnT-III and the other enzymes to the cancer progression are in conflict with each other. While GnT-III prevents cancer, the others increase metastasis. The function of FUT8 is related to signal transduction and its activity is higher in tumor tissue than in healthy tissue. The impact of glycosylation changes on some of the cancer-associated proteins (growth factor receptors, adhesion and signal molecules, CD147, TIMP-1, and matriptase) is also summarized.

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“…Several mechanisms have been proposed to explain the regulation of CD147 expression, including the following mechanisms: the TGF-β1-CD147 signalling loop in the development of liver fibrosis; the regulatory loop involving miR-22, Sp1, and c-Myc modulating CD147 expression; and the induction of CD147 clustering by galectin-3192021. Among the various mechanisms, the modification of CD147 by N-glycosylation has been demonstrated to be instrumental for the regulation of CD147 function during malignant transformation22. Previous studies have suggested that CD147 deglycosylation by tunicamycin treatment not only results in a failure to induce MMP-1 and MMP-2 expression, but also inhibits the induction of MMPs secretion caused by native CD14723.…”

mentioning

confidence: 99%

N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: promoting tumour metastasis in hepatocellular carcinoma

Huang

Peng

et al. 2016

Sci Rep

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Cluster of differentiation 147 (CD147), also known as extracellular matrix metalloproteinase inducer, is a transmembrane glycoprotein that mediates oncogenic processes partly through N-glycosylation modifications. N-glycosylation has been demonstrated to be instrumental for the regulation of CD147 function during malignant transformation. However, the role that site-specific glycosylation of CD147 plays in its defective function in hepatocellular carcinomacells needs to be determined. Here, we demonstrate that the modification of N-glycosylation at Asn152 on CD147 strongly promotes hepatocellular carcinoma (HCC) invasion and migration. After the removal of N-glycans at Asn152, CD147 was more susceptible to degradation by ER-localized ubiquitin ligase-mediated endoplasmic reticulum-associated degradation (ERAD). Furthermore, N-linked glycans at Asn152 were required for CD147 to acquire and maintain proper folding in the ER. Moreover, N-linked glycans at Asn152 functioned as a recognition motif that was directly mediated by the CNX quality control system. Two phases in the retention-based ER chaperones system drove ER-localized CD147 trafficking to degradation. Deletion of N-linked glycosylation at Asn152 on CD147 significantly suppressed in situ tumour metastasis. These data could potentially shed light on the molecular regulation of CD147 through glycosylation and provide a valuable means of developing drugs that target N-glycans at Asn152 on CD147.

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Importance of N-Glycosylation on CD147 for Its Biological Functions

Cited by 95 publications

References 120 publications

Identification of Cell Surface Straight Chain Poly-N-Acetyl-Lactosamine Bearing Protein Ligands for VH4-34–Encoded Natural IgM Antibodies

Identification of Cell Surface Straight Chain Poly-N-Acetyl-Lactosamine Bearing Protein Ligands for VH4-34–Encoded Natural IgM Antibodies

Glycosylation changes leading to the increase in size on the common core of N-glycans, required enzymes, and related cancer-associated proteins

N-linked glycosylation at Asn152 on CD147 affects protein folding and stability: promoting tumour metastasis in hepatocellular carcinoma

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