Evolutionary and functional implications of the complex glycosylation of XXXX , a cytoplasmic/nuclear glycoprotein associated with polyubiquitination.

@entity1 @entity2734 @entity3913 @entity70164 @entity10783 @entity4826 @entity6826 @entity11066 @entity19447 @entity3363 @entity72449
Protein degradation is regulatory for the cell cycle, signal transduction and gene transcription. A critical step is the selective marking of the target protein, resulting in polyubiquitination by one of a large number of E3-ubiquitin ligases. Both target marking and E3-ubiquitin ligase activity are associated with common as well as unusual posttranslational modifications. For example, hydroxylation of Pro-residues and modification of @entity2734 -residues by high- @entity3913 sugar chains can target the modified proteins for rapid polyubiquitination in the @entity1 cytoplasm. Both @entity10783 hydroxylation and glycosylation also occur on @entity11066 , a subunit of the @entity6826 class of E3-ubiquitin ligases, from Dictyostelium. In this case, a pentasaccharide containing Gal, Fuc and N-acetyl-D-glucosmine ( @entity4826 ) is attached to the HyPro-residue. The @entity3363 are added sequentially by enzymes that reside in the cytoplasm rather than the secretory pathway. Two of the glycosyltransferases appear to be positioned in ancient evolutionary lineages that bridge prokaryotes and eukaryotes. The first, which attaches @entity4826 to HyPro, is related to enzymes that form @entity70164 - and @entity72449 -Ser/Thr linkages in the Golgi. @entity4826 is extended by a bifunctional glycosyltransferase that mediates the ordered addition of beta1,3-linked @entity19447 and alpha1,2-linked Fuc, using an architecture resembling that of two-domain prokaryotic glycosyltransferases involved in glycosaminoglycan synthesis. Mutational and pharmacological perturbation of glycosylation alters the subcellular localization of Skpl and growth properties ofcells. @entity10783 hydroxylation and complex O-glycosylation provide the cell with new options for epigenetic regulation of protein turnover in its cytoplasmic and nuclear compartments.
