Laboratory of Biology, School of Medicine, University of Patras, 26505 Rio, Patras, Greece.
J Biol Chem. 2011 Jul 1;286(26):23234-46. doi: 10.1074/jbc.M110.207688. Epub 2011 May 4.
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.
多细胞生物的发育和稳态依赖于细胞增殖和分化之间的精细平衡。Geminin 通过直接结合并抑制 DNA 复制许可因子 Cdt1 来调节细胞周期。Geminin 还与分化的转录调节剂和染色质重塑因子相互作用,其平衡相互作用与发育过程中的增殖-分化决策有关。在这里,我们描述了 Idas(Idas 在古希腊神话中是 Gemini 的表亲),一种以前未被表征的与 Geminin 相关的卷曲螺旋蛋白。我们表明,人源 Idas 定位于细胞核,通过卷曲螺旋介导的相互作用在细胞内和体外与 Geminin 形成复合物,并可以改变 Geminin 的亚细胞定位。Idas 不与 Cdt1 结合,并且在体外阻止 Geminin 与 Cdt1 结合。细胞中 Idas 的耗竭会影响细胞周期进程;细胞在 S 期积累,并且无法有效地进入有丝分裂。Idas 蛋白水平在后期下降,而过表达会导致有丝分裂缺陷。在发育过程中,我们表明 Idas 在小鼠端脑的脉络丛和皮质区高度表达。我们的数据突出了 Idas 作为一种新的 Geminin 结合伴侣,参与细胞周期进程,并可能是发育过程中增殖-分化决策的调节剂。