title: Role of Geminin in cell fate determination of hematopoietic stem cells (HSCs).
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).
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan. syasunag@fukuoka-u.ac.jp.|Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan. syasunag@fukuoka-u.ac.jp.
authors.forename: Shin'ichiro
authors.identifier: http://orcid.org/0000-0001-7163-7891
authors.initials: S
authors.lastname: Yasunaga
authors.affiliation: Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ohno
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Shirasu
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suzuki-Takedachi
authors.affiliation: Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.|Department of Food and Fermentation Science, Faculty of Food Science and Nutrition, Beppu University, 82 Kitaishigaki, Beppu, Oita, 874-0915, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Ohtsubo
authors.affiliation: Department of Stem Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takihara
mesh_terms: D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D064248:Geminin / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000473:pathology
chemical_list: D064248:Geminin
keywords: Cell fate determination; Differentiation; Geminin; Hematopoietic stem cells (HSCs); Self-renewal