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J. Biol. Chem., Vol. 277, Issue 37, 33604-33609, September 13, 2002
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From the Center for Immunotherapy of Cancer and Infectious
Diseases, University of Connecticut School of Medicine,
Farmington, Connecticut 06030-1601
Hsp70 and Hsc70 are two chaperones of high
homology expressed under contrasting situations. Hsc70 is
constitutively expressed and poorly stress-inducible, whereas Hsp70 is
unabundant in normal physiological situations and strongly induced
under oxidative stress. In the present study we show that the
chaperoning activity of purified Hsp70 and Hsc70 is minimal under
reducing conditions and increases in environments that mimic oxidative
stress. Association with peptides is more pronounced for Hsp70 than for
Hsc70 in every condition tested and is accompanied with a gradual
change in secondary structure during oxidation. The binding of peptides
to Hsp70 and Hsc70 under oxidative conditions is not reversible by
treatment with a reducing agent, confirming that other
chaperone-associated factors are required for substrate release. These
findings support the idea that formation of HSP70-peptide complexes and
possibly their immunogenicity is enhanced in conditions of stress.
Differential Acquisition of Antigenic Peptides by Hsp70 and
Hsc70 under Oxidative Conditions*
,
,
,
*
Dr. Ménoret has a financial interest in Antigenics
Inc. The University of Connecticut is aware of this potential conflict of interest. Further information is available from Dr. A. Ménoret.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.
These authors contributed equally to this work and are listed in
alphabetical order.
§
Current address: Dept. of Laboratory Medicine, Yale University, New
Haven, CT 06520-8035.
¶
Supported by Grant RO1CA/AI84042 from the National Institutes
of Health. To whom correspondence should be addressed. Tel.: 860-679-4248; Fax: 860-679-6512; E-mail: menoret@up.uchc.edu.
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