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Volume 271, Number 23, Issue of June 7, 1996 pp. 13697-13705
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

Molecular Cloning and Characterization of Lysosomal Sialic Acid O-Acetylesterase

(Received for publication, February 7, 1996)

M. Jorge Guimarães Dagger , J. Fernando Bazan Dagger , Janice Castagnola , Sandra Diaz , Neal G. Copeland par , Debra J. Gilbert par , Nancy A. Jenkins par , Ajit Varki and Albert Zlotnik Dagger

From the Dagger  DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304, the  Glycobiology Program, University of California at San Diego Cancer Center, La Jolla, California 92093-0063, and the par  ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Frederick, Maryland 21702

O-Acetylation and de-O-acetylation of sialic acids have been implicated in the regulation of a variety of biological phenomena, including endogenous lectin recognition, tumor antigenicity, virus binding, and complement activation. Applying a strategy designed to identify genes preferentially expressed in active sites of embryonic hematopoiesis, we isolated a novel cDNA from the pluripotent hematopoietic cell line FDCPmixA4 whose open reading frame contained sequences homologous to peptide fragments of a lysosomal sialic acid O-acetylesterase (Lse) previously purified from rat liver, but with no evident similarity to endoplasmic reticulum-derived acetylesterases. The expressed Lse protein exhibits sialic-acid O-acetylesterase activity that is not attributable to a typical serine esterase active site. lse expression is spatially and temporally restricted during embryogenesis, and its mRNA levels correlate with differences in O-acetylesterase activity described in adult tissues and blood cell types. Using interspecific backcross analysis, we further mapped the lse gene to the central region of mouse chromosome 9. This constitutes the first report on the molecular cloning of a sialic acid-specific O-acetylesterase in vertebrates and suggests novel roles for the 9-O-acetyl modification of sialic acids during the development and differentiation of mammalian organisms.


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