生物谷报道：自我更新和分异之间的平衡是干细胞和癌症生物学的基础。果蝇神经干细胞通过非对称细胞分裂做到这一点，在非对称细胞分裂期间，影响自我更新和分异的因素被非均等地隔离。现在，Wang等人发现，有丝分裂激酶Polo通过磷酸化Pon（Numb的接头蛋白）调控肿瘤抑制蛋白Numb的非对称定位。Polo通过调控Pon/Numb来起一个肿瘤抑制剂的作用。这些发现表明在细胞周期与非对称蛋白定位之间存在一个直接的生化联系，同时也揭示了一个新颖的肿瘤抑制机制。
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: bingwei@stanford.edu) or W.C. (Email: wchia@tll.org.sg).
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.
