Isolation and characterization of cytoplasmic cyclin D1 mutants

Murakami, Hirokazu; Horihata, Minoru; Andojo, Satoru; Yoneda-Kato, Noriko; Kato, Jun-ya

doi:10.1016/j.febslet.2009.04.036

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Volume 583, Issue 10 , Pages 1575-1580, 19 May 2009

Isolation and characterization of cytoplasmic cyclin D1 mutants

Edited by Angel Nebrada

Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan

Received 8 February 2009; received in revised form 17 April 2009; accepted 19 April 2009. published online 29 April 2009.

Abstract

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.