Inhibition of genotoxic stress induced apoptosis by novel TAT-fused peptides targeting PIDDosome

Title
Inhibition of genotoxic stress induced apoptosis by novel TAT-fused peptides targeting PIDDosome
Author(s)
박현호장태호이성준우창훈이태진이경진[이경진]전주홍[전주홍]이동섭[이동섭]최기항[최기항]김인규[김인규]김영환[김영환]
Keywords
NF-KAPPA-B; DEATH DOMAIN SUPERFAMILY; INDUCED-PROXIMITY MODEL; CASPASE ACTIVATION; DNA-DAMAGE; CELL-DEATH; CANCER THERAPEUTICS; PIDD; PROTEIN; MECHANISM
Issue Date
201201
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
BIOCHEMICAL PHARMACOLOGY, v.83, no.2, pp.218 - 227
Abstract
Genotoxic stress induced apoptosis is mediated by the formation of PIDDosome, which is a caspase-2 activating complex composed of three protein components, PIDD, RAIDD, and caspase-2. Here, synthetic TAT-fused peptides designed by the structure of PIDD and RAIDD, TAT-Y814A and TAT-R147E, respectively, were produced and tested for their ability to inhibit PIDDosome formation in vitro as well as to attenuate genotoxic stress-induced apoptosis in human renal cancer cells. The results show that TAT-Y814A and TAT-R147E have the potential to inhibit formation of the PIDDosome in a dose-dependent manner. Furthermore, both peptides partially inhibit genotoxic stress mediated apoptosis and activation of caspase2 and caspase3 in Caki cells. These results suggest that TAT-Y814A (also TAT-R147E) is a novel inhibitor of genotoxic stress-induced apoptosis that may serve as a prototype for anti-apoptotic drug development. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/30041http://dx.doi.org/10.1016/j.bcp.2011.10.013
ISSN
0006-2952
Appears in Collections:
이과대학 > 화학생화학부 > Articles
생명공학부 > 생명공학부 > Articles
의과대학 > 약리학교실 > Articles
의과대학 > 해부학교실 > Articles
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