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

Tae Ho Jang, Sung Jun Lee, Chang Hoon Woo, Kyung Jin Lee, Ju Hong Jeon, Dong Sup Lee, Kihang Choi, In Gyu Kim, Young Whan Kim, Tae Jin Lee, Hyun Ho Park

Research output: Contribution to journalArticle

3 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)218-227
Number of pages10
JournalBiochemical Pharmacology
Volume83
Issue number2
DOIs
Publication statusPublished - 2012 Jan 15

Keywords

  • Apoptosis
  • Caspase-2
  • Cisplatin
  • PIDD
  • PIDDosome
  • RAIDD
  • TAT-fused peptides.

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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  • Cite this

    Jang, T. H., Lee, S. J., Woo, C. H., Lee, K. J., Jeon, J. H., Lee, D. S., Choi, K., Kim, I. G., Kim, Y. W., Lee, T. J., & Park, H. H. (2012). Inhibition of genotoxic stress induced apoptosis by novel TAT-fused peptides targeting PIDDosome. Biochemical Pharmacology, 83(2), 218-227. https://doi.org/10.1016/j.bcp.2011.10.013