Core 1 β3galactosyltransferase (C1GalT1, T-synthase) and its specific molecular chaperone cosmc (C1GalT1C1)

Abstract

Core 1 UDP-Gal: N-acetylgalactosaminyl-α1-O-Ser/Thr β3galactosyltransferase (core 1 β3galactosyltransferase, core 1 β3GalT, C1GALT1, T-synthase, EC 2.4.1.122) transfers the Gal from UDP-Gal to N-acetylgalactosaminyl-α1-O-Ser/Thr (Tn antigen) in a protein to form Galβ1,3GalNAc-a-Ser/Thr, the core 1 structure also known as T antigen (Fig. 15.1) in the mucin-type O-glycosylation pathway. This core 1 structure is the most common precursor for a variety of complex structures of mucin-type O-glycans (O-glycans) usually found in many mucins, membrane glycoproteins, and secreted glycoproteins (Ju et al. 2011a). These O-glycans include mono- and di-sialyl core 1, sialyl Lewis x (SLeX) core 2 O-glycans with or without poly-N-acetyllactosamine structures, and extended core 1 O-glycans with sulfation such as sulfo-sialyl Lewis x (MECA79 epitope). The O-glycans on glycoproteins play important roles in immunity (Ellies et al. 1998; Homeister et al. 2001; Yeh et al. 2001), cell-cell interactions (selectins and their ligands) (Homeister et al. 2001; Leppanen et al. 1999; McEver et al. 1995; Wilkins et al. 1996; Yeh et al. 2001), vascular biology (Tenno et al. 2007), angiogenesis (Xia et al. 2004), lymphangiogenesis (Fu et al. 2008), and biogenesis and function of platelets (Wang et al. 2012). Biochemically and biologically, T-synthase is the key glycosyltransferase in the biosynthesis and biology of mucin-type O-glycan.