Structure, pathology and function of the N-linked sugar chains of human chorionic gonadotropin

被引:43
作者
Kobata, A
Takeuchi, M
机构
[1] Tokyo Metropolitan Inst Gerontol, Itabashi Ku, Tokyo 1730015, Japan
[2] Kirin Brewery Co Ltd, Cent Lab, Yokohama, Kanagawa 2360004, Japan
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 1999年 / 1455卷 / 2-3期
关键词
human chorionic gonadotropin; N-linked sugar chains; N-acetylglucosaminyltransferase IV; choriocarcinoma; hydatidiform mole; invasive mole;
D O I
10.1016/S0925-4439(99)00060-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human chorionic gonadotropin (hCG) contains five acidic N-linked sugar chains, which are derived from three neutral oligosaccharides by sialylation. Each of the two subunits (hCG alpha and hCG beta) of hCG contain two glycosylated Asn residues. Glycopeptides, each containing a single glycosylated Asn, were obtained by digestion of hCG alpha with trypsin, and of hCG beta with chymotrypsin and lysyl endopeptidase. Comparative study of the sugar chains of the four glycopeptides revealed the occurrence of site-directed glycosylation. Studies of the sugar chains of hCGs, purified from urine of patients with various trophoblastic diseases, revealed that choriocarcinoma hCGs contain sialylated or non-sialylated forms of eight neutral oligosaccharides. In contrast, hCGs from invasive mole patients contain sialyl derivatives of five neutral oligosaccharides. The structural characteristics of the five neutral oligosaccharides, detected in choriocarcinoma hCGs but not in normal placental hCGs, indicate that N-acetylglucosaminyltransferase IV (GnT-IV) is abnormally expressed in the malignant cells. This supposition was confirmed by molecular biological study of GnT-IV in placenta and choriocarcinoma cell lines. The appearance of tumor-specific sugar chains in hCG has been used to develop a diagnostic method of searching for malignant trophoblastic diseases. In addition, a summary of the current knowledge concerning the functional role of N-linked sugar chains in the expression of the hormonal activity of hCG has been presented. (C) 1999 Elsevier Science B.V. All rights reserved.
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页码:315 / 326
页数:12
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