title: Idas, a novel phylogenetically conserved geminin-related protein, binds to geminin and is required for cell cycle progression.
abstract: Development and homeostasis of multicellular organisms relies on an intricate balance between cell proliferation and differentiation. Geminin regulates the cell cycle by directly binding and inhibiting the DNA replication licensing factor Cdt1. Geminin also interacts with transcriptional regulators of differentiation and chromatin remodelling factors, and its balanced interactions are implicated in proliferation-differentiation decisions during development. Here, we describe Idas (Idas being a cousin of the Gemini in Ancient Greek Mythology), a previously uncharacterised coiled-coil protein related to Geminin. We show that human Idas localizes to the nucleus, forms a complex with Geminin both in cells and in vitro through coiled-coil mediated interactions, and can change Geminin subcellular localization. Idas does not associate with Cdt1 and prevents Geminin from binding to Cdt1 in vitro. Idas depletion from cells affects cell cycle progression; cells accumulate in S phase and are unable to efficiently progress to mitosis. Idas protein levels decrease in anaphase, whereas its overexpression causes mitotic defects. During development, we show that Idas exhibits high level expression in the choroid plexus and the cortical hem of the mouse telencephalon. Our data highlight Idas as a novel Geminin binding partner, implicated in cell cycle progression, and a putative regulator of proliferation-differentiation decisions during development.
authors.affiliation: Laboratory of Biology, School of Medicine, University of Patras, 26505 Rio, Patras, Greece.
authors.forename: Dafni-Eleutheria
authors.initials: DE
authors.lastname: Pefani
authors.forename: Maria
authors.initials: M
authors.lastname: Dimaki
authors.forename: Magda
authors.initials: M
authors.lastname: Spella
authors.forename: Nickolas
authors.initials: N
authors.lastname: Karantzelis
authors.forename: Eirini
authors.initials: E
authors.lastname: Mitsiki
authors.forename: Christina
authors.initials: C
authors.lastname: Kyrousi
authors.forename: Ioanna-Eleni
authors.initials: IE
authors.lastname: Symeonidou
authors.forename: Anastassis
authors.initials: A
authors.lastname: Perrakis
authors.forename: Stavros
authors.initials: S
authors.lastname: Taraviras
authors.forename: Zoi
authors.initials: Z
authors.lastname: Lygerou
mesh_terms: D000595:Amino Acid Sequence; D000705:Anaphase / Q000502:physiology; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002831:Choroid Plexus / Q000166:cytology / Q000196:embryology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D064248:Geminin; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D016196:S Phase / Q000502:physiology; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors
chemical_list: C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C577995:GMNN protein, human; D064248:Geminin; C577997:Gmnn protein, mouse; C560898:MCIDAS protein, human; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C498645:Ris2 protein, mouse; D014157:Transcription Factors