Isolation and characterization of cytoplasmic cyclin D1 mutants.
To elucidate the mechanism governing the subcellular distribution of cyclin D1 protein, we randomly mutagenized human cyclin D1 cDNA and isolated mutants that encode the protein predominantly located in the cytoplasm. Experiments with Leptomycin B suggested a defect in transportation from the cytoplasm to the nucleus rather than enhanced nuclear exportation. Sequencing revealed that the mutations responsible for the cytoplasmic localization of cyclin D1 resided in the vicinity of the cyclin box, which affected interaction with a catalytic partner, Cdk4. We propose that interaction between cyclin D1 and Cdk4 triggers the mechanism controlling the nuclear transportation of this kinase complex.
Murakami
Hirokazu
H
Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara, Japan.
Horihata
Minoru
M
Andojo
Satoru
S
Yoneda-Kato
Noriko
N
Kato
Jun-ya
JY
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D018076:DNA, Complementary / Q000737:chemistry; D006801:Humans; D051379:Mice; D016296:Mutagenesis; D009154:Mutation; D041681:NIH 3T3 Cells; D014162:Transfection
C530104:CCND1 protein, human; D018076:DNA, Complementary; D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4