A soybean cDNA encoding a chromatin-binding peptide inhibits mitosis of mammalian cells.
A soybean cDNA encoding the small subunit peptide of a cotyledon-specific 2S albumin (Gm2S-1) is thought to play a role in arresting mitosis during the DNA endoreduplication and cell expansion phase of seed development. The peptide (termed lunasin) contains the cell adhesion motif Arg-Gly-Asp (RGD) followed by eight aspartic acid residues at its C-terminal end. A chimeric gene encoding the lunasin peptide tagged with green fluorescent protein (GFP) arrested cell division, caused abnormal spindle fiber elongation, chromosomal fragmentation, and cell lysis when transiently transfected into murine embryo fibroblast, murine hepatoma, and human breast cancer cells. Deletion of the polyaspartyl end abolished the antimitotic effect. Subcellular localization of lunasin and immunobinding assay using synthetic peptides revealed the preferential adherence of lunasin to chromatin. Immunofluorescence showed that kinetochore proteins were displaced from the centromere in lunasin-transfected cells. These observations suggest that lunasin binds to the chromatin, leading to disruption of kinetochore formation and inhibition of mitosis.
Galvez
A F
AF
Division of Nutritional Sciences and Toxicology, University of California, Berkeley 94720-3104, USA.
de Lumen
B O
BO
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D053938:DNA Fragmentation; D018076:DNA, Complementary; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D051379:Mice; D008938:Mitosis / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000235:genetics / Q000494:pharmacology; D010940:Plant Proteins / Q000235:genetics* / Q000494:pharmacology; D030262:Soybean Proteins; D013025:Glycine max / Q000235:genetics* / Q000502:physiology; D014162:Transfection
D002843:Chromatin; D018076:DNA, Complementary; C120514:GM2S-1 protein, soybean; D010455:Peptides; D010940:Plant Proteins; D030262:Soybean Proteins