title: Inhibition of genotoxic stress induced apoptosis by novel TAT-fused peptides targeting PIDDosome.
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.
authors: Graduate School of Biochemistry at Yeungnam University, Gyeongsan, South Korea.
authors: Tae-Ho
authors: TH
authors: Jang
authors: Sung-Jun
authors: SJ
authors: Lee
authors: Chang-Hoon
authors: CH
authors: Woo
authors: Kyung Jin
authors: KJ
authors: Lee
authors: Ju-Hong
authors: JH
authors: Jeon
authors: Dong-Sup
authors: DS
authors: Lee
authors: Kihang
authors: K
authors: Choi
authors: In-Gyu
authors: IG
authors: Kim
authors: Young Whan
authors: YW
authors: Kim
authors: Tae-Jin
authors: TJ
authors: Lee
authors: Hyun Ho
authors: HH
authors: Park
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics*; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015696:Gene Products, tat / Q000235:genetics / Q000502:physiology*; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D053418:Death Domain Receptor Signaling Adaptor Proteins; D015696:Gene Products, tat; C485896:PIDD1 protein, human; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins