title: Caspase-3 cleaves the formin-homology-domain-containing protein FHOD1 during apoptosis to generate a C-terminal fragment that is targeted to the nucleolus.
abstract: The formin homology (FH) proteins play a crucial role in cytoskeleton remodelling during many essential processes. In this study, we demonstrate for the first time that the formin-homology-domain-containing protein FHOD1 is cleaved by caspase-3 at the SVPD(616) site during apoptosis. Using confocal microscopy, we further demonstrate that while full length FHOD1 is mostly cytoplasmic, the FHOD1 N-terminal cleavage product is diffusely localized throughout the cytoplasm and the nucleoplasm, whereas the C-terminal cleavage product is almost exclusively nuclear with some nucleolar localization. Finally, using a run-on transcription assay we show that the C-terminal FHOD1 cleavage product has the ability to inhibit RNA polymerase I transcription when overexpressed in HeLa cells as shown by blockage of BrUTP incorporation.
authors.affiliation: Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada, H3G 1Y6.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ménard
authors.forename: François G
authors.initials: FG
authors.lastname: Gervais
authors.forename: Donald W
authors.initials: DW
authors.lastname: Nicholson
authors.forename: Sophie
authors.initials: S
authors.lastname: Roy
mesh_terms: D020816:Amino Acid Motifs; D017209:Apoptosis; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D002466:Cell Nucleolus / Q000378:metabolism*; D018076:DNA, Complementary; D005326:Fetal Proteins / Q000737:chemistry / Q000378:metabolism*; D000080865:Formins; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D012318:RNA Polymerase I / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D018076:DNA, Complementary; C120021:FHOD1 protein, human; D005326:Fetal Proteins; D000080865:Formins; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012318:RNA Polymerase I; C505407:CASP3 protein, human; D053148:Caspase 3