Suppression of receptor-mediated apoptosis by death effecter domain recruiting domain binding peptide aptamer.
FLASH protein is a component of death-inducing signaling complex and might be involved in death receptor-mediated extrinsic apoptosis. Here we developed the peptide aptamer against death effecter domain recruiting domain (DRD) of FLASH protein and showed that the peptide bound to FLASH protein in vitro. Intracellular expression of the DRD-binding peptide aptamer specifically suppressed receptor-mediated extrinsic apoptosis but not intrinsic pathway, which was recapitulated by the antisense oligonucleotides for FLASH. These data suggest that DRD-binding peptide is not only a novel inhibitor modulating receptor-mediated apoptosis but also a tool for elucidating the roles of FLASH in apoptosis.
Kim
Gab Seok
GS
Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Republic of Korea.
Park
Young Ae
YA
Choi
Yong Seok
YS
Choi
Yun-Hee
YH
Choi
Hyun Woo
HW
Jung
Yong-Keun
YK
Jeong
Sunjoo
S
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology*; D052158:Aptamers, Peptide / Q000302:isolation & purification / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019151:Peptide Library; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D020349:Surface Plasmon Resonance; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048069:Tumor Necrosis Factors / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D052158:Aptamers, Peptide; C485604:CASP8AP2 protein, human; D002135:Calcium-Binding Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D016376:Oligonucleotides, Antisense; D019151:Peptide Library; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases