Caspase-3 cleaved p65 fragment dampens NF-kappa B-mediated anti-apoptotic transcription by interfering with the p65/RPS3 interaction

摘要

Caspase-3-mediated p65 cleavage is believed to suppress nuclear factor-kappa B (NF-kappa B)-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-kappa B transactivation. Here we show that the p65(1-97) fragment generated by Caspase-3 cleavage interferes with ribosomal protein S3 (RPS3), an NF-kappa B "specifier" subunit, and selectively retards the nuclear translocation of RPS3, thus dampening the RPS3/NF-kappa B-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-kappa B-conferred anti-apoptotic transcription by the fragment from partial p65 cleavage by activated Caspase-3. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.