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Originally published In Press as doi:10.1074/jbc.M207637200 on December 27, 2002
J. Biol. Chem., Vol. 278, Issue 10, 8572-8579, March 7, 2003
Apoptosis in Leukemia Cells Is Accompanied by Alterations in the
Levels and Localization of Nucleolin*
Yingchang
Mi ,
Shelia D.
Thomas ,
Xiaohua
Xu ,
Lavona K.
Casson ,
Donald M.
Miller §, and
Paula J.
Bates §¶
From the Molecular Targets Group, James Graham Brown Cancer Center,
Departments of Medicine and
§ Biochemistry/Molecular Biology, University of
Louisville, Louisville, Kentucky 40202
Molecular defects in apoptotic pathways
are thought to often contribute to the abnormal expansion of malignant
cells and their resistance to chemotherapy. Therefore, a comprehensive
knowledge of the mechanisms controlling induction of apoptosis and
subsequent cellular disintegration could result in improved methods for
prognosis and treatment of cancer. In this study, we have examined
apoptosis-induced alterations in two proteins, nucleolin and
poly(ADP-ribose) polymerase-1 (PARP-1), in U937 leukemia cells.
Nucleolin is expressed at high levels in malignant cells, and it is a
multifunctional and mobile protein that can shuttle among the
nucleolus, nucleoplasm, cytoplasm, and plasma membrane. Here, we report
our findings that UV irradiation or camptothecin treatment of U937
cells induced apoptosis and caused a significant change in the
levels and localization of nucleolin within the nucleus. Additionally,
nucleolin levels were dramatically decreased in extracts containing the
cytoplasm and plasma membrane. These alterations could be abrogated by
pre-incubation with an inhibitor of PARP-1 (3-aminobenzamide), and our
data support a potential role for nucleolin in removing cleaved PARP-1
from dying cells. Furthermore, both nucleolin and cleaved PARP-1 were detected in the culture medium of cells undergoing apoptosis, associated with particles of a size consistent with apoptotic bodies.
These results indicate that nucleolin plays an important role in
apoptosis, and could be a useful marker for assessing apoptosis or
detecting apoptotic bodies. In addition, the data provide a possible
explanation for the appearance of nucleolin and PARP-1
autoantibodies in some autoimmune diseases.
*
This work was supported by Department of Defense Grants
DAMD17-01-1-0067 (to P. J. B.) and DAMD17-98-1-8583 (to
D. M. M.), the Commonwealth of Kentucky Research Challenge
Trust, and the James Graham Brown Cancer Center.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
To whom correspondence should be addressed: 204B Baxter
Bldg., 570 S. Preston St., Louisville, KY 40202. Tel.: 502-852-2432; Fax: 502-852-2356; E-mail: paula.bates@louisville.edu.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
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