Identification of the sequence responsible for the nuclear localization of human Cdc6.
The Cdc6 is the essential protein for the initiation of DNA replication. Cdc6 is localized in the G1 nucleus, and abnormal nuclear localization of this protein induces irregular initiation of DNA replication. We identified here that amino acids K57 and R58 in the human Cdc6 protein play an important role in the nuclear localization of the protein. The fundamental features of the mechanism regulating the localization of Cdc6 seem to be maintained in yeast, Xenopus, and human, since the amino acid sequence surrounding K57 and R58, (S/T)PXKR(L/I), is conserved in these species. Substitution of amino acid residue S54 with E and not Q blocked partially the nuclear localization of the protein, implying that the phosphorylation at S54 is involved in the regulating mechanism of the cell cycle-dependent localization of Cdc6.
Takei
Y
Y
Division of Molecular Cell Pharmacology, National Children's Medical Research Center, Tokyo, Japan.
Yamamoto
K
K
Tsujimoto
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D004261:DNA Replication; D018076:DNA, Complementary / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014982:Xenopus laevis
C066503:CDC6 protein, S cerevisiae; C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D005656:Fungal Proteins; D019913:Nuclear Localization Signals; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins