Inhibition of genotoxic stress induced apoptosis by novel TAT-fused peptides targeting PIDDosome
- Authors
- Jang, Tae-Ho; Lee, Sung-Jun; Woo, Chang-Hoon; Lee, Kyung Jin; Jeon, Ju-Hong; Lee, Dong-Sup; Choi, Kihang; Kim, In-Gyu; Kim, Young Whan; Lee, Tae-Jin; Park, Hyun Ho
- Issue Date
- 15-1월-2012
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- Apoptosis; Caspase-2; RAIDD; PIDD; PIDDosome; Cisplatin; TAT-fused peptides
- Citation
- BIOCHEMICAL PHARMACOLOGY, v.83, no.2, pp.218 - 227
- Indexed
- SCIE
SCOPUS
- Journal Title
- BIOCHEMICAL PHARMACOLOGY
- Volume
- 83
- Number
- 2
- Start Page
- 218
- End Page
- 227
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/109076
- DOI
- 10.1016/j.bcp.2011.10.013
- ISSN
- 0006-2952
- 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.
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