Regulation of geminin functions by cell cycle-dependent nuclear-cytoplasmic shuttling (Mol Cell Biol, 2007, 27:4737-4744)

報告日期: 2007/11/13
報告時間: 15:10/16:00
報告學生: 李定遠
講評老師: 何中良
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Regulation of Geminin Functions by Cell Cycle-Dependent

Nuclear-Cytoplasmic Shuttling

 

Mol Cell Biol. 2007 Jul;27(13):4737-44

 

Speaker:李定遠

Commentator:何中良 醫師

Date11/13, 15:00-16:00

Abstract

The Geminin protein functions both as a DNA re-replication inhibitor and as a repressor of Hox gene transcription1. Geminin inhibits DNA re-replication by preventing the loading of MCM (minichromosome maintenance) complex onto chromatin. Geminin also associates transiently with members of the Hox-repressing polycomb complex to repress the Hox gene transcription2. It is know that geminin is inactivated at the end of mitosis by APC (anaphase promoting complex) mediated degradation. However, the evidence in Xenopus oocytes showed a significant part of geminin resists degradation at the end of mitosis, suggesting a novel mechanism regulating geminin activity independent of degradation. In this report, the authors demonstrate that geminin shuttles into nuclei in S phase and inhibits the loading of the MCM complex and Hox gene transcription. At the end of mitosis, geminin is exported from nuclei to the cytoplasm by the exportin protein Crm1 and is unavailable in the nucleus during the next G1 phase, thus securing association loading of the MCM complex on chromatin and the transcription of Hox gene. In this paper, the authors provide a regulating mechanism of geminin that is distinct from protein degradation and ubiquitination.

 

References

1.     Luo L, Kessel M. Geminin coordinates cell cycle and developmental control. Cell Cycle. 2004;3:711-714.

2.     Luo L, Yang X, Takihara Y, Knoetgen H, Kessel M. The cell-cycle regulator geminin inhibits Hox function through direct and polycomb-mediated interactions. Nature. 2004;427:749-753.