title: A thermally targeted peptide inhibitor of symmetrical dimethylation inhibits cancer-cell proliferation.
abstract: Targeting splicing machinery components is an underdeveloped strategy for cancer therapy. Uridine-rich small nuclear ribonucleoproteins (UsnRNPs) are essential spliceosome components that recognize splice sites in newly transcribed RNA. The major spliceosomal snRNPs are comprised of UsnRNA bound by a ring of Sm proteins. The survival of motor neuron (SMN) complex provides specificity for binding of Sm proteins to UsnRNAs. Three of the seven proteins that comprise the Sm core possess post-translationally modified C-terminal symmetric dimethylarginine (sDMA) residues which promote binding of these proteins to SMN. Here we describe a peptide inhibitor of sDMA that is capable of interfering with SMN/SmB interaction. The inhibitory peptide was attached to elastin-like polypeptide, a thermally responsive macromolecular carrier, in order to increase its stability and allow enhancement of its cellular uptake by thermal targeting. The fusion polypeptide inhibited the interaction of SMN/SmB, inhibited proliferation, and induced apoptosis in HeLa cells.
authors.affiliation: Department of Biochemistry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
authors.forename: Gene L
authors.initials: GL
authors.lastname: Bidwell
authors.forename: Angela A
authors.initials: AA
authors.lastname: Whittom
authors.forename: Emily
authors.initials: E
authors.lastname: Thomas
authors.forename: Daniel
authors.initials: D
authors.lastname: Lyons
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hebert
authors.forename: Drazen
authors.initials: D
authors.lastname: Raucher
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D008745:Methylation / Q000187:drug effects*; D051379:Mice; D018613:Microscopy, Confocal; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D010455:Peptides