Peptide binding to Geminin and inhibitory for DNA replication.
Geminin binds to Cdt1 to ensure that DNA replication occurs only once during the cell cycle. To identify the peptide that binds to Geminin and thereby modifies the latter's ability to alter the DNA replication activity in human cancer cells, we screened a phage display library of random peptides in successive cycles of phage library panning and found one peptide sequence that bound to the 31-111 amino acid residues of Geminin. Delivery of this peptide sequence into the nucleus of HCT116 human colon cancer cells resulted in the suppression of BrdU incorporation. These results provide new insights into the function of Geminin and further validate Geminin as a potential therapeutic target in tumors.
Yoshida
Kenichi
K
Division of Genetic Diagnosis, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. yoshidak@ims.u-tokyo.ac.jp
Inoue
Ituro
I
D000595:Amino Acid Sequence; D001973:Bromodeoxyuridine / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D004247:DNA / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects* / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D018604:Epitope Mapping; D004926:Escherichia coli / Q000378:metabolism; D064248:Geminin; D045325:HCT116 Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection
C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C577995:GMNN protein, human; D064248:Geminin; D009842:Oligopeptides; D019151:Peptide Library; D011994:Recombinant Proteins; D004247:DNA; D001973:Bromodeoxyuridine