The human Cas1 protein: a sialic acid-specific O-acetyltransferase?
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.
Department of Molecular Biology, University Salzburg, Austria.
Sigrid
S
Arming
Dirk
D
Wipfler
Juliane
J
Mayr
Anette
A
Merling
Ulrike
U
Vilas
Roland
R
Schauer
Reinhard
R
Schwartz-Albiez
Reinhard
R
Vlasak
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D002238:Carbohydrate Epimerases / Q000378:metabolism*; D020134:Catalytic Domain; D002460:Cell Line; D003001:Cloning, Molecular; D057225:Data Mining; D055785:Gene Knockdown Techniques; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D016415:Sequence Alignment; D013379:Substrate Specificity; D015854:Up-Regulation
D000123:Acetyltransferases; D002238:Carbohydrate Epimerases; D019158:N-Acetylneuraminic Acid; C561597:CASD1 protein, human; C544542:dermatan sulfate epimerase 1, mouse