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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
,
J. Fernando
Bazan
,
Janice
Castagnola
¶
,
Sandra
Diaz
¶
,
Neal G.
Copeland
,
Debra J.
Gilbert
,
Nancy A.
Jenkins
,
Ajit
Varki
¶
and
Albert
Zlotnik
From the 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 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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Copyright © 1996 by the American Society for Biochemistry and Molecular Biology.
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