title: Caspase-3 cleaved p65 fragment dampens NF-κB-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-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.
authors.affiliation: Department of Biochemistry and Molecular Biology, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wier
authors.affiliation: Department of Biochemistry and Molecular Biology, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, USA; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21025, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hodgson
authors.affiliation: Department of Biochemistry and Molecular Biology, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, USA; Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD 21287, USA. Electronic address: fwan1@jhu.edu.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Wan
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D012269:Ribosomal Proteins / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D010446:Peptide Fragments; D012269:Ribosomal Proteins; D051996:Transcription Factor RelA; C044152:ribosomal protein S3; D053148:Caspase 3
keywords: Apoptosis; Caspase-3 cleavage; Fate determination; Gene transcription; Nuclear factor-kappa B; Ribosomal protein S3