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Molecular and Cellular Biology, July 2007, p. 4626-4640, Vol. 27, No. 13
0270-7306/07/$08.00+0     doi:10.1128/MCB.00862-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Cyclin D2 Translocates p27 out of the Nucleus and Promotes Its Degradation at the G0-G1 Transition{triangledown}

Etsuo Susaki,1,2 Keiko Nakayama,2,3 and Keiichi I. Nakayama1,2*

Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan,1 CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan,2 Department of Developmental Biology, Center for Translational and Advanced Animal Research, Graduate School of Medicine, Tohoku University, 2-1 Seiryo, Aoba-ku, Sendai 980-8575, Japan3

Received 15 May 2006/ Returned for modification 15 June 2006/ Accepted 10 April 2007

The nuclear export and cytoplasmic degradation of the cyclin-dependent kinase inhibitor p27 are required for effective progression of the cell cycle through the G0-G1 transition. The mechanism responsible for this translocation of p27 has remained unclear, however. We now show that cyclin D2 directly links growth signaling with the nuclear export of p27 at the G0-G1 transition in some cell types. The up-regulation of cyclin D2 in response to mitogenic stimulation was found to occur earlier than that of other D-type cyclins and in parallel with down-regulation of p27 at the G0-G1 transition. RNA interference-mediated depletion of cyclin D2 inhibited the nuclear export of p27 and delayed its degradation at the G0-G1 transition. In contrast, overexpression of cyclin D2 in G0 phase shifted the localization of p27 from the nucleus to the cytoplasm and reduced the stability of p27. Overexpression of the cyclin D2(T280A) mutant, whose export from the nucleus is impaired, prevented the translocation and degradation of p27. These results indicate that cyclin D2 translocates p27 from the nucleus into the cytoplasm for its KPC-dependent degradation at the G0-G1 transition.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-6815. Fax: 81-92-642-6819. E-mail: nakayak1{at}bioreg.kyushu-u.ac.jp

{triangledown} Published ahead of print on 23 April 2007.

Molecular and Cellular Biology, July 2007, p. 4626-4640, Vol. 27, No. 13
0270-7306/07/$08.00+0     doi:10.1128/MCB.00862-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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