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Suzuki-Anekoji M.,Glycobiology Unit | Suzuki A.,Glycobiology Unit | Suzuki A.,Keio University | Wu S.-W.,Academia Sinica, Taiwan | And 10 more authors.
Journal of Biological Chemistry | Year: 2013

Background: Chst10 transfers sulfate to glucuronic acid to form the HNK-1 antigen carried by glycoproteins and glycolipids in neurons and NK cells. Results: Chst10 transfers sulfate to glucuronidated steroid hormones, and Chst10-deficient mice exhibited subfertility. Conclusion: Subfertility in Chst10 null females is caused by a loss of steroid hormone dysregulation. Significance: This study identified a new regulatory mechanism mediated by sulfation of glucuronidated steroid.© 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Yoneyama T.,Glycobiology Unit | Yoneyama T.,Hirosaki University | Angata K.,Glycobiology Unit | Angata K.,Japan National Institute of Advanced Industrial Science and Technology | And 5 more authors.
Molecular Biology of the Cell | Year: 2012

Glycans of α-dystroglycan (α-DG), which is expressed at the epithelial cell-basement membrane (BM) interface, play an essential role in epithelium development and tissue organization. Laminin-binding glycans on α-DG expressed on cancer cells suppress tumor progression by attenuating tumor cell migration from the BM. However, mechanisms controlling laminin-binding glycan expression are not known. Here, we used small interfering RNA (siRNA) library screening and identified Fer kinase, a non-receptor-type tyrosine kinase, as a key regulator of laminin-binding glycan expression. Fer overexpression decreased laminin- binding glycan expression, whereas siRNA-mediated down-regulation of Fer kinase increased glycan expression on breast and prostate cancer cell lines. Loss of Fer kinase function via siRNA or mutagenesis increased transcription levels of glycosyltransferases, including protein O-mannosyltransferase 1, β3-N-acetylglucosaminyltransferase 1, and like-acetylglucosaminyltransferase that are required to synthesize laminin-binding glycans. Consistently, inhibition of Fer expression decreased cell migration in the presence of laminin fragment. Fer kinase regulated STAT3 phosphorylation and consequent activation, whereas knockdown of STAT3 increased laminin-binding glycan expression on cancer cells. These results indicate that the Fer pathway negatively controls expression of genes required to synthesize lamininbinding glycans, thus impairing BM attachment and increasing tumor cell migration. © 2012 Yoneyama et al.

Yoneyama T.,Hirosaki University | Hatakeyama S.,Hirosaki University | Tobisawa Y.,Hirosaki University | Yamamoto H.,Hirosaki University | And 11 more authors.
Transplantation | Year: 2013

Background: Antibody-mediated rejection after ABO-incompatible kidney transplantation (ABO-I KTx) is a major barrier to transplantation success. The advent of immunosuppressive therapy has markedly improved graft survival in ABO-I KTx. However, compared with normal KTx, clinical conditions during ABO-I KTx are difficult to control because of overimmunosuppression. To reduce the need for immunosuppression, we aimed to develop a novel blood group antigen-neutralizing therapy. Methods: We screened for an ABO blood group antigen-targeting peptide (BATP) by screening of T7 phage-displayed peptide library. After screening, hemagglutination inhibition assays, enzyme-linked immunosorbent assay, and cytotoxicity assay were used to analyze the blood group antigen-blocking effect and toxicity of BATP. We also tested the inhibitory effects on anti-blood group antibody binding in normal human kidney tissues blocked with BATP and excised kidneys perfused ex vivo with BATP. Results: We identified six peptide sequences that efficiently suppressed hemagglutination of red blood cells by anti-ABO blood group antibodies and binding of these antibodies to ABO histo-blood group antigens in kidney tissues. Surprisingly, ex vivo perfusion of BATP in kidneys excised from renal cell carcinoma patients caused significant suppression of anti-blood group antibody binding to antigen and IgG and IgM deposition in renal glomerular capillaries after ABO-I blood reperfusion. Conclusions: These data indicate that A/B blood group antigens on red blood cells and in kidney tissues may be neutralized by BATP. This approach may enable the development of a novel blood group antigen-neutralizing therapy to overcome the challenges of ABO-I KTx. © 2013 Lippincott Williams & Wilkins.

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