Cyclin D2 translocates p27 out of the nucleus and promotes its degradation at the G0-G1 transition

Etsuo Susaki, Keiko Nakayama, Keiichi I. Nakayama

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)4626-4640
Number of pages15
JournalMolecular and cellular biology
Volume27
Issue number13
DOIs
Publication statusPublished - Jul 1 2007

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Cyclin D2
Cell Nucleus Active Transport
Cytoplasm
Cyclin-Dependent Kinase Inhibitor p27
Cyclin D
Cell Cycle Resting Phase
RNA Interference
Cell Cycle
Up-Regulation
Down-Regulation
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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Cyclin D2 translocates p27 out of the nucleus and promotes its degradation at the G0-G1 transition. / Susaki, Etsuo; Nakayama, Keiko; Nakayama, Keiichi I.

In: Molecular and cellular biology, Vol. 27, No. 13, 01.07.2007, p. 4626-4640.

Research output: Contribution to journalArticle

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