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

Eric M. Wier, Kai Fu, Andrea Hodgson, Xin Sun, Fengyi Wan

Research output: Contribution to journalArticlepeer-review

Abstract

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 p651-97 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.

Original languageEnglish (US)
Pages (from-to)3581-3587
Number of pages7
JournalFEBS Letters
Volume589
Issue number23
DOIs
StatePublished - Nov 30 2015

Keywords

  • Apoptosis
  • Caspase-3 cleavage
  • Fate determination
  • Gene transcription
  • Nuclear factor-kappa B
  • Ribosomal protein S3

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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