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01-09-2016 | Review Article

Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs)

Authors: Shin’ichiro Yasunaga, Yoshinori Ohno, Naoto Shirasu, Bo Zhang, Kyoko Suzuki-Takedachi, Motoaki Ohtsubo, Yoshihiro Takihara

Published in: International Journal of Hematology | Issue 3/2016

Abstract

Geminin exerts two distinct molecular roles. Geminin negatively regulates DNA replication licensing through the direct interaction with Cdt1 to prevent re-replication in proliferating cells. Geminin also regulates chromatin remodeling through the direct interaction with Brahma/Brg1 to maintain undifferentiated states of stem cells. We previously uncovered that Polycomb-group complex 1 and Hoxb4/Hoxa9, well-known intrinsic factors that are essential for maintaining the hematopoietic stem cell (HSC) activity, alternatively act as ubiquitin–proteasome systems for Geminin protein to reduce the protein expression level, and sustain the HSC activity. Thus, Geminin is presumed to play an important role in determining cell fate, i.e., turning on and off cellular quiescence and proliferation/differentiation, in HSCs. We recently generated recombinant cell-penetrating Geminin (CP-Geminin), enabling rapid incorporation and withdraw of Geminin protein in cells. CP-Geminin may be useful in regulating the cell cycle and chromatin configuration. In this article, we summarize current information on the molecular functions of Geminin and the regulatory system for Geminin protein expression, and argue for the molecular role of Geminin in cell fate determination of HSCs, and future perspective of a new technology for manipulating the activities of HSCs and cancer stem cells (CSCs).

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Title: Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs)
Authors: Shin’ichiro Yasunaga
Yoshinori Ohno
Naoto Shirasu
Bo Zhang
Kyoko Suzuki-Takedachi
Motoaki Ohtsubo
Yoshihiro Takihara
Publication date: 01-09-2016
Publisher: Springer Japan
Published in: International Journal of Hematology / Issue 3/2016
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI: https://doi.org/10.1007/s12185-016-2060-9

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