生物谷報(bào)道：自我更新和分異之間的平衡是干細(xì)胞和癌癥生物學(xué)的基礎(chǔ)。果蠅神經(jīng)干細(xì)胞通過非對稱細(xì)胞分裂做到這一點(diǎn),，在非對稱細(xì)胞分裂期間,，影響自我更新和分異的因素被非均等地隔離。現(xiàn)在,，Wang等人發(fā)現(xiàn),，有絲分裂激酶Polo通過磷酸化Pon（Numb的接頭蛋白）調(diào)控腫瘤抑制蛋白Numb的非對稱定位。Polo通過調(diào)控Pon/Numb來起一個(gè)腫瘤抑制劑的作用,。這些發(fā)現(xiàn)表明在細(xì)胞周期與非對稱蛋白定位之間存在一個(gè)直接的生化聯(lián)系,，同時(shí)也揭示了一個(gè)新穎的腫瘤抑制機(jī)制。
英文原文：
Nature 449, 96-100 (6 September 2007) | doi:10.1038/nature06056; Received 28 May 2007; Accepted 28 June 2007
Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon
Hongyan Wang1,3, Yingshi Ouyang2,3, W. Gregory Somers1, William Chia1 & Bingwei Lu2
Temasek Life Sciences Laboratory and Department of Biological Sciences, National University of Singapore, Singapore 117604
Department of Pathology, Stanford University School of Medicine, Geriatric Research, Education and Clinical Center (GRECC)/VA Palo Alto Health Care System (VAPAHCS), Palo Alto, California 94304, USA
These authors contributed equally to this work.
Correspondence to: William Chia1Bingwei Lu2 Correspondence and requests for materials should be addressed to B.L. (Email: [email protected]) or W.C. (Email: [email protected]).
Self-renewal and differentiation are cardinal features of stem cells. Asymmetric cell division provides one fundamental mechanism by which stem cell self-renewal and differentiation are balanced1, 2. A failure of this balance could lead to diseases such as cancer3, 4, 5, 6. During asymmetric division of stem cells, factors controlling their self-renewal and differentiation are unequally segregated between daughter cells. Numb is one such factor that is segregated to the differentiating daughter cell during the stem-cell-like neuroblast divisions in Drosophila melanogaster7, where it inhibits self-renewal8, 9. The localization and function of Numb is cell-cycle-dependent7, 10, 11, 12. Here we show that Polo (ref. 13), a key cell cycle regulator, the mammalian counterparts of which have been implicated as oncogenes as well as tumour suppressors14, 15, acts as a tumour suppressor in the larval brain. Supernumerary neuroblasts are produced at the expense of neurons in polo mutants. Polo directly phosphorylates Partner of Numb (Pon, ref. 16), an adaptor protein for Numb, and this phosphorylation event is important for Pon to localize Numb. In polo mutants, the asymmetric localization of Pon, Numb and atypical protein kinase C are disrupted, whereas other polarity markers are largely unaffected. Overexpression of Numb suppresses neuroblast overproliferation caused by polo mutations, suggesting that Numb has a major role in mediating this effect of Polo. Our results reveal a biochemical link between the cell cycle and the asymmetric protein localization machinery, and indicate that Polo can inhibit progenitor self-renewal by regulating the localization and function of Numb.
