Mechanism of the immunomodulatory activity of glycodelin.
Glycodelin, a progesterone regulated protein synthesized by the endometrium (GdA) has been well documented to inhibit the proliferation of activated T-cells and is an indispensable molecule in the maternal system for the establishment, maintenance and progression of pregnancy. Data from our laboratory have unequivocally shown that the immunosuppression by GdA is via induction of apoptosis in activated T cells. Another isoform of glycodein, GdS, from the male reproductive system, in spite of sharing an identical amino acid sequence as that of GdA has been shown not to harbour the immunosuppressive activity of GdA. As the only difference between the two proteins is glycosylation, we proposed to study the role of the sugars in imparting apoptotic activity to Gd. Using the recombinant baculovirus system, Gd lacking glycosylation was expressed and from the experimental observations we could conclude that the activity of Gd lies in the protein backbone. Recombinant Gd expressed in P. pastoris, and Chinese hamster ovary cells, like the GdS did not exhibit apoptotic activity. A close analyses of the glycans associated with the Gd molecules from various sources suggested that though the apoptogenic activity of Gd lies in the protein backbone, the glycans modulate the activity by masking (as in case of GdS and most recombinant Gd expressed in our laboratory) or unmasking (as in case of GdA and baculovirus expressed Gd), the functional region of the molecule.
Karande
Anjali A
AA
Department of Biochemistry, Indian Institute of Science, Bangalore.
Mukhopadhyay
Debaditya
D
Jayachandran
Rajesh
R
Sundarraj
Swathi
S
Alok
Anshula
A
D000328:Adult; D000818:Animals; D017209:Apoptosis; D001212:Asialoglycoproteins / Q000494:pharmacology; D016367:Baculoviridae / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D011257:Pregnancy Proteins / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D001212:Asialoglycoproteins; D000071816:Glycodelin; D006023:Glycoproteins; D007166:Immunosuppressive Agents; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D011994:Recombinant Proteins