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Molecular and Cellular Biology, July 2000, p. 4648-4657, Vol. 20, No. 13
Apoptogen Inc.; Solange Gauthier Karsh
Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario;
and Department of Biochemistry, Microbiology and Immunology, University
of Ottawa, Ottawa, Ontario K1H 8L1, Canada
Received 9 February 2000/Returned for modification 22 March
2000/Accepted 11 April 2000
X-linked inhibitor of apoptosis protein (XIAP) is a key regulator
of programmed cell death triggered by various apoptotic triggers.
Translation of XIAP is controlled by a 162-nucleotide (nt) internal
ribosome entry site (IRES) element located in the 5' untranslated
region of XIAP mRNA. XIAP IRES mediates
efficient translation of XIAP under physiological stress and enhances
cell protection against serum deprivation and radiation-induced
apoptosis. In the present report we describe the assembly of a
sequence-specific RNA-protein complex consisting of at least four
cytosolic proteins on the XIAP IRES element. We determine
that the core binding sequence is approximately 28 nt long and is
located 34 nt upstream of the initiation site. Moreover, we identify
the La autoantigen as a protein that specifically binds
XIAP IRES in vivo and in vitro. The biological relevance of
this interaction is further demonstrated by the inhibition of
XIAP IRES-mediated translation in the absence of functional
La protein. The results suggest an important role for the La protein in
the regulation of XIAP expression, possibly by facilitating ribosome
recruitment to the XIAP IRES.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Functional Characterization of the X-Linked
Inhibitor of Apoptosis (XIAP) Internal Ribosome Entry Site Element:
Role of La Autoantigen in XIAP Translation
*
Corresponding author. Mailing address: Solange Gauthier
Karsh Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario Research Institute, 401 Smyth Road, Room R306, Ottawa, Ontario
K1H 8L1, Canada. Phone: (613) 738-3821. Fax: (613) 738-4833. E-mail:
bob{at}mgcheo.med.uottawa.ca.
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