Oligosaccharides modulate the apoptotic activity of glycodelin

Jayachandran, Rajesh and Radcliffe, Catherine M and Royle, Louise and Harvey, David J and Dwek, Raymond A. and Rudd, Pauline M and Karande, Anjali A (2006) Oligosaccharides modulate the apoptotic activity of glycodelin. In: Glycobiology, 16 (11). pp. 1052-1063.

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Abstract

GlycodelinA (GdA), a multifunctional glycoprotein secreted at high concentrations by the uterine endometrium during the early phases of pregnancy, carries glycan chains on asparagines at positions N28 and N63. GdA purified from amniotic fluid is known to be a suppressor of T-cell proliferation, an inducer of T-cell apoptosis, and an inhibitorof sperm-zona binding in contrast to its glycoform, glycodelinS (GdS), which is secreted by the seminal vesicles into the seminal plasma. The oligosaccharide chains of GdA terminate in sialic acid residues, whereas those of GdS are not sialylated but are heavily fucosylated. Our previous work has shown that the apoptogenic activity of GdA resides in the protein backbone, and we have also demonstrated the importance of sialylation for the manifestation of GdA-induced apoptosis. Recombinant glycodelin (Gd) expressed in the Sf21 insec cell line yielded an apoptotically active Gd; however, the same geneexpressed in the insect cell line Tni produced apoptotically inactive Gd, as observed with the gene expressed in the Chinese hamster ovary(CHO) cell line and earlier in Pichia pastoris. Glycan analysis of the Tni and Sf21 cell line-expressed Gd proteins reveals differences in their glycan structures, which modulate the manifestation of apoptogenic activity of Gd. Through apoptotic assays carried out with the wild-type (WT) and glycosylation mutants of Gd expressed in Sf21 and Tni cells before and after mannosidase digestion, we conclude that the accessibility to the apoptogenic region of Gd is influenced by the size of the glycans.

Item Type:	Journal Article
Publication:	Glycobiology
Publisher:	Oxford University Press
Additional Information:	Copyright of this article belongs to Oxford University Press.
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	04 Aug 2010 05:08
Last Modified:	19 Sep 2010 06:12
URI:	http://eprints.iisc.ac.in/id/eprint/30802

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