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Caspase‐3 cleaved p65 fragment dampens NF‐κB‐mediated anti‐apoptotic transcription by interfering with the p65/RPS3 interaction
Author(s) -
Wier Eric M.,
Fu Kai,
Hodgson Andrea,
Sun Xin,
Wan Fengyi
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.10.019
Subject(s) - transactivation , apoptosis , transcription factor , microbiology and biotechnology , cleavage (geology) , chemistry , protein subunit , nf κb , transcription (linguistics) , caspase 8 , caspase , p50 , biology , programmed cell death , gene , biochemistry , linguistics , philosophy , paleontology , fracture (geology)
Caspase‐3‐mediated p65 cleavage is believed to suppress nuclear factor‐kappa B (NF‐κB)‐mediated anti‐apoptotic transactivation in cells undergoing apoptosis. However, only a small percentage of p65 is cleaved during apoptosis, not in proportion to the dramatic reduction in NF‐κB transactivation. Here we show that the p65 1‐97 fragment generated by Caspase‐3 cleavage interferes with ribosomal protein S3 (RPS3), an NF‐κB “specifier” subunit, and selectively retards the nuclear translocation of RPS3, thus dampening the RPS3/NF‐κB‐dependent anti‐apoptotic gene expression. Our findings reveal a novel cell fate determination mechanism to ensure cells undergo programed cell death through interfering with RPS3/NF‐κB‐conferred anti‐apoptotic transcription by the fragment from partial p65 cleavage by activated Caspase‐3.