O-glycosylation of nuclear and cytoplasmic proteins: Regulation analogous to phosphorylation?

Glycoproteins are classically thought of as components of the plasma membrane and extracellular spaces. The notion that glycoproteins occur in the nuclear and/or cytoplasmic portions of the cell has only recently gained wide acceptance. The resistance of the biochemical community to accept the existence of nuclear and cytoplasmic glycoproteins has stemmed from the fact that our understanding of the structure and biosynthesis of classical N- and O-linked oligosaccharide modifications of proteins is quite advanced. One tenet which is basic to our knowledge of these glycoproteins is that saccharides are added to proteins only in the lumen of the endoplasmic reticulum and Golgi apparatus (1,2). Thus, the classic model of biosynthesis predicts that the carbohydrate portions of glycoproteins are in a topologically distinct compartment from the cytoplasm and nucleus and occur only in the lumen of the endoplasmic reticulum and Golgi apparatus, on the cell surface, or in the extracellular spaces (1). In spite of this apparent ''dogma'', a large body of data from numerous laboratories in the past decade has confirmed the presence of glycoproteins in the nucleus and cytoplasm (3-5).