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Director: Fernando Irazoqui

PhD Thesis Topic

Biosynthesis and degradation of O-GalNAc type glycans in the cell nucleus

O-GalNAc type glycan biosynthesis is a post-translational modification of proteins that carry out multiple glycosyltransferases (GTs) that act in a coordinated manner. The O-GalNAc-type glycosylation start step is catalyzed by polypeptidyl GalNAc-transferases (GalNAc-Ts), there are 20 isoforms in humans with proven enzymatic activity. These enzymes allow the covalent attachment of α-N-acetylgalactosamine (α-GalNAc) in the Ser / Thr residues of the proteins, generating a structure known as Tn antigen. This structure is extended by the addition of numerous monosaccharides by the action of specific GTs. Tumor cells commonly express altered levels of O-GalNAc-type glycans, and the aberrant biosynthesis of these O-glycans represents one of the frequent post-translational changes associated with cancer. In many tumor tissues it has been observed that the expression of the Tn antigen and related structures such as Sialil-Tn, T antigen and Sialil-T are increased, while they are absent or rarely expressed in normal tissues.