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Blood, Vol. 95 No. 8 (April 15), 2000:
pp. 2593-2599
Transcriptional control of the human plasma membrane
phospholipid scramblase 1 gene is mediated by
interferon-
Quansheng Zhou,
Ji Zhao,
Fahad Al-Zoghaibi,
Aimin Zhou,
Therese Wiedmer,
Robert H. Silverman, and
Peter J. Sims
From the Department of Molecular and Experimental Medicine and
Department of Vascular Biology, The Scripps Research Institute, La
Jolla, California; and the Department of Cancer Biology, Lerner
Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
Interferons (IFNs) mediate their diverse biologic activities through
induction of the expression of multiple genes. Whereas the mode of
action of certain of these IFN-regulated genes has been well
characterized, most of the molecular and cellular events underlying the
constellation of biologic responses to the IFNs remain unresolved. This
study showed that the newly identified PLSCR1 gene for
phospholipid scramblase, previously implicated in remodeling of plasma
membrane phospholipids, is regulated at the transcriptional level by
IFN- . Analysis of 5' flanking genomic sequence in reporter
constructs showed that transcriptional control of PLSCR1 was
entirely regulated by a single IFN-stimulated response element located
in the first exon. A similar induction of PLSCR1 by IFN-2a
was also observed in a variety of other human tumor cell lines as well
as in human umbilical vein endothelial cells. In these cell lines, the
marked IFN-2a-induced increase in PLSCR1 protein expression,
ranging as high as 10-fold above basal levels, was not accompanied by
increased cell surface exposure of phosphatidylserine, suggesting that
remodeling of the cell surface requires both exposure to IFN and a
second yet-to-be identified event to stimulate plasma membrane
phospholipid scramblase activity and to mobilize phosphatidylserine to
the cell surface.
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