Cyclin D2 translocates p27 out of the nucleus and promotes its degradation at the G0-G1 transition.
The nuclear export and cytoplasmic degradation of the cyclin-dependent kinase inhibitor p27 are required for effective progression of the cell cycle through the G(0)-G(1) 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 G(0)-G(1) 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 G(0)-G(1) transition. RNA interference-mediated depletion of cyclin D2 inhibited the nuclear export of p27 and delayed its degradation at the G(0)-G(1) transition. In contrast, overexpression of cyclin D2 in G(0) 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 G(0)-G(1) transition.
Susaki
Etsuo
E
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Nakayama
Keiko
K
Nakayama
Keiichi I
KI
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D056742:Cyclin D2; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D016193:G1 Phase; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008954:Models, Biological; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D016192:Resting Phase, Cell Cycle; D015854:Up-Regulation / Q000235:genetics
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D010769:Phosphothreonine; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6