The human Cas1 protein: A sialic acid-specific O-acetyltransferase?

Abstract

Sialic acids are important sugars at the reducing end of glycoproteins and glycolipids. They are among many other functions involved in cell-cell interactions, host-pathogen recognition and the regulation of serum half-life of glycoproteins. An important modification of sialic acids is O-acetylation, which can alter or mask the biological properties of the parent sialic acid molecule. The nature of mammalian sialate-O-acetyltransferases (EC 2.3.1.45) involved in their biosynthesis is still unknown. We have identified the human CasD1 (capsule structure1 domain containing 1) gene as a candidate to encode the elusive enzyme. The human CasD1 gene encodes a protein with a serine-glycine-asparagine-histidine hydrolase domain and a hydrophobic transmembrane domain. Expression of the Cas1 protein tagged with enhanced green fluorescent protein in mammalian and insect cells directed the protein to the medial and trans-cisternae of the Golgi. Overexpression of the Cas1 protein in combination with α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (GD3 synthase) resulted in an up to 40% increased biosynthesis of 7-O-acetylated ganglioside GD3. By quantitative real-time polymerase chain reaction, we found up to 5-fold increase in CasD1 mRNA in tumor cells overexpressing O-Ac-GD3. CasD1-specific small interfering RNA reduced O-acetylation in tumor cells. These results suggest that the human Cas1 protein is directly involved in O-acetylation of α2-8-linked sialic acids.

Molecular Design of Boronic Acid-Functionalized Squarylium Cyanine Dyes for Multiple Discriminant Analysis of Sialic Acid in Biological Samples: Selectivity toward Monosaccharides Controlled by Different Alkyl Side Chain Lengths

“…Under these conditions, the signal of H-10 (in the 2-position of the PBA group) was a singlet (see Figure 4c), as was the case for the signal of H-10 in the spectrum of monomeric SQ-BA2 in DMSO-d 6 . This fact suggests that the Fru−SQ-BA2 complex exists as a one-to-one, emissive, monomeric species in aqueous solution.…”

“…The NMR spectra were obtained using a JEOL ECX-400 spectrometer operated at 400 MHz and a Bruker AVANCE500T spectrometer operated at 500 MHz for 1 H. Chemical shifts are reported in parts per million downfield from tetramethylsilane as the internal standard in DMSO-d 6 .…”

Loss-of-Function Mutation of REDUCED WALL ACETYLATION2 in Arabidopsis Leads to Reduced Cell Wall Acetylation and Increased Resistance to Botrytis cinerea

“…The bioinformatics study of Anantharaman and Aravind (2010) indicated that the C-terminal domain of Cas1p and the plant RWA proteins belong to a larger class of acyltransferases with 10 transmembrane helices, whereas the N-terminal domain is an esterase domain. Another recent study showed that overexpression of the human Cas1 homolog in mammalian cells led to increased O-acetylation of sialic acid (Arming et al, 2010), suggesting that metazoan Cas1 homologs are sialic acid O-acetyltransferases. Sialyltransferase and overexpressed human Cas1 were shown to be colocalized in Golgi vesicles (Arming et al, 2010).…”

“…Another recent study showed that overexpression of the human Cas1 homolog in mammalian cells led to increased O-acetylation of sialic acid (Arming et al, 2010), suggesting that metazoan Cas1 homologs are sialic acid O-acetyltransferases. Sialyltransferase and overexpressed human Cas1 were shown to be colocalized in Golgi vesicles (Arming et al, 2010). Interestingly, it is known that mammalian O-acetylation of sialic acid takes place inside the Golgi vesicles by an integral membrane protein that utilizes acetyl-CoA from the cytoplasm to form an acetylated intermediate and releases CoA back into the cytoplasm (Higa et al, 1989).…”

Reduced Wall Acetylation Proteins Play Vital and Distinct Roles in Cell Wall O-Acetylation in Arabidopsis

“…According to this model, different RWA proteins may preferentially form complexes with a subset of TBL proteins. However, even in animals, it is not clear how the Cas1 protein mediates acetylation of sialic acid, and while Cas1 is definitely required, the acetylation could involve additional proteins (Arming et al, 2011).…”