VATIS UPDATE Article

In a study scientists at the University of Georgia, the United States, have shown that a rare type of glycosylation greatly affects the function of a protein important for human development and cancer progression. The research team of Dr. Robert Haltiwanger, has studied specific O-linked modifications, i.e., the attachment of glucose or fucose to serine or threonine, a modification that affects only a few hundred different types of proteins, including one called Notch.

It’s a signaling receptor critical for cell development and differentiation and is dysregulated in cancers such as leukemia, breast cancer, and prostate cancer. The enzymes responsible for modifying Notch with glucose and fucose are called POFUT1 and POGLUT1. Dr. Haltiwanger’s team, led by Dr. Hideyuki Takeuchi, wanted to know exactly why POFUT1 and POGLUT1 were attaching glucose and fucose to Notch in cells.

The finding of the study has been published in the Journal of Biological Chemistry. “Here we demonstrate that cell-surface expression of endogenous Notch1 in HEK293T cells is dependent on the presence of POGLUT1 and POFUT1 in an additive manner. In vitro unfolding assays reveal that addition of O-glucose or O-fucose stabilizes a single EGF repeat, and that addition of both O-glucose and O-fucose enhances stability in an additive manner,” wrote the investigators.