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

ABSTRACT: Caspase-3-mediated p65 cleavage is believed to suppress nuclear factor-kappa B (NF-?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-?B transactivation. Here we show that the p65(1-97) fragment generated by Caspase-3 cleavage interferes with ribosomal protein S3 (RPS3), an NF-?B "specifier" subunit, and selectively retards the nuclear translocation of RPS3, thus dampening the RPS3/NF-?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-?B-conferred anti-apoptotic transcription by the fragment from partial p65 cleavage by activated Caspase-3.

SUBMITTER: Wier EM 

PROVIDER: S-EPMC4655178 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature