Abstract:
:Autophagy defects have recently been associated with chromosomal instability, a hallmark of human cancer. However, the functional specificity and mechanism of action of autophagy-related factors in genome stability remain elusive. Here we report that UVRAG, an autophagic tumor suppressor, plays a dual role in chromosomal stability, surprisingly independent of autophagy. We establish that UVRAG promotes DNA double-strand-break repair by directly binding and activating DNA-PK in nonhomologous end joining. Disruption of UVRAG increases genetic instability and sensitivity of cells to irradiation. Furthermore, UVRAG was also found to be localized at centrosomes and physically associated with CEP63, an integral component of centrosomes. Disruption of the association of UVRAG with centrosomes causes centrosome instability and aneuploidy. UVRAG thus represents an autophagy-related molecular factor that also has a convergent role in patrolling both the structural integrity and proper segregation of chromosomes, which may confer autophagy-independent tumor suppressor activity.
journal_name
Dev Celljournal_title
Developmental cellauthors
Zhao Z,Oh S,Li D,Ni D,Pirooz SD,Lee JH,Yang S,Lee JY,Ghozalli I,Costanzo V,Stark JM,Liang Cdoi
10.1016/j.devcel.2011.12.027subject
Has Abstractpub_date
2012-05-15 00:00:00pages
1001-16issue
5eissn
1534-5807issn
1878-1551pii
S1534-5807(12)00136-0journal_volume
22pub_type
杂志文章abstract::In yeast and animal cells, the sterol composition of membranes is a key factor that controls the polarity of membrane proteins by regulating their intracellular trafficking or lateral diffusion. A recent study in Nature Cell Biology demonstrates that plant sterols play a major role in the acquisition of cell polarity ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2008.02.007
更新日期:2008-03-01 00:00:00
abstract::Asymmetric cell divisions generate cellular diversity. In Drosophila, embryonic neuroblasts target cell fate determinants basally, rotate their spindles by 90 degrees to align with the apical-basal axis, and divide asymmetrically in a stem cell-like fashion. In this process, apically localized Bazooka recruits Inscute...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00020-0
更新日期:2003-02-01 00:00:00
abstract::Metazoans express three unfolded protein response transducers (IRE1, PERK, and ATF6) ubiquitously to cope with endoplasmic reticulum (ER) stress. ATF6 is an ER membrane-bound transcription factor activated by ER stress-induced proteolysis and has been duplicated in mammals. Here, we generated ATF6alpha- and ATF6beta-k...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.07.018
更新日期:2007-09-01 00:00:00
abstract::Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in various embryonic and adult tissues. Mice mutant for either Tet1 or Tet2 are viable, raising the question of whether these enzymes have overlapping roles in development. Here we have generated Tet1 and Tet2 double-knockout (DKO)...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.12.015
更新日期:2013-02-11 00:00:00
abstract::Zebrafish is a powerful model for forward genetics. Reverse genetic approaches are limited by the time required to generate stable mutant lines. We describe a system for gene knockout that consistently produces null phenotypes in G0 zebrafish. Yolk injection of sets of four CRISPR/Cas9 ribonucleoprotein complexes redu...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.06.003
更新日期:2018-07-02 00:00:00
abstract::Trunk neural crest cells are generated at the border between the neural plate and nonneural ectoderm, where they initiate a distinct program of gene expression, undergo an epithelial-mesenchymal transition (EMT), and delaminate from the neuroepithelium. Here, we provide evidence that members of three families of trans...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2004.12.010
更新日期:2005-02-01 00:00:00
abstract::Rab GTPases define the vesicle trafficking pathways underpinning cell polarization and migration. Here, we find that Rab4, Rab11, and Rab14 and the candidate Rab GDP-GTP exchange factors (GEFs) FAM116A and AVL9 are required for cell migration. Rab14 and its GEF FAM116A localize to and act on an intermediate compartmen...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.04.010
更新日期:2012-05-15 00:00:00
abstract::We show that Rap2, a member of the Ras GTPase family, positively regulates Activin/Nodal signaling activity by controlling the trafficking of its receptors. In the absence of ligand activation, Rap2 directs internalized Activin/Nodal receptors into a recycling pathway, thereby preventing their degradation and maintain...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2008.05.004
更新日期:2008-07-01 00:00:00
abstract::To ensure equal chromosome segregation during mitosis, the macromolecular kinetochore must remain attached to depolymerizing microtubules, which drive chromosome movements. How kinetochores associate with depolymerizing microtubules, which undergo dramatic structural changes forming curved protofilaments, has yet to b...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.09.012
更新日期:2012-11-13 00:00:00
abstract::The orientation of the mitotic spindle plays a key role in determining whether a polarized cell will divide symmetrically or asymmetrically. In most cell types, cytoplasmic dynein plays a critical role in spindle orientation. However, how dynein directs opposite spindle poles toward distinct and predetermined cell end...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2006.02.018
更新日期:2006-04-01 00:00:00
abstract::Appropriate axonal growth and connectivity are essential for functional wiring of the brain. Joubert syndrome-related disorders (JSRD), a group of ciliopathies in which mutations disrupt primary cilia function, are characterized by axonal tract malformations. However, little is known about how cilia-driven signaling r...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2019.11.005
更新日期:2019-12-16 00:00:00
abstract::Reporting in Developmental Cell, Pereira et al. (2016) use in vitro lineage reprogramming insights to inform understanding of hematopoietic stem cell (HSC) development in vivo. They find Prom1(+)Sca1(+)CD34(+)CD45(-) hemogenic precursors, akin to fibroblast-derived hemato-vascular precursors, in mouse placenta and emb...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2016.02.022
更新日期:2016-03-07 00:00:00
abstract::Vascular endothelial growth factor (VEGF) and Angiopoietin 1 (Ang1) are both potent proangiogenic factors, but, whereas VEGF causes vascular permeability, Ang1 stabilizes blood vessels and protects them from VEGF-induced plasma leakage. The antivascular permeability mechanisms deployed by Ang1 are still undefined. Her...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.10.019
更新日期:2008-01-01 00:00:00
abstract::Successive cell divisions during embryonic cleavage create increasingly smaller cells, so intracellular structures must adapt accordingly. Mitotic spindle size correlates with cell size, but the mechanisms for this scaling remain unclear. Using live cell imaging, we analyzed spindle scaling during embryo cleavage in t...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.04.022
更新日期:2018-05-21 00:00:00
abstract::Boundary formation and epithelialization are crucial processes in the morphological segmentation of vertebrate somites. By a genetic screening procedure with zebrafish, we identified two genes, integrinalpha5 (itga5) and fibronectin (fn), required for these processes. Fibronectin proteins accumulate at somite boundari...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2005.03.006
更新日期:2005-04-01 00:00:00
abstract::Studies of myoblast fusion in Drosophila have revealed numerous signaling and structural proteins that regulate this critical event in muscle development. A paper by Chen et al. published in the September 19 issue of Cell adds ARF6, a GTPase, and one of its guanine nucleotide exchange factors to this set of players. ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00298-3
更新日期:2003-10-01 00:00:00
abstract::Reactive oxygen species (ROS), despite having damaging roles, serve as signaling molecules regulating diverse biological and physiological processes. Employing in vivo genetic studies in Drosophila, we show that besides causing G1-S arrest by activation of Dacapo, ROS can simultaneously inhibit cell growth by regulati...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2019.04.008
更新日期:2019-05-06 00:00:00
abstract::Lipid droplets are fat storage organelles in cells that physically resemble stable oil-water emulsion droplets. In this issue of Developmental Cell, Ben M'barek et al. (2017) show that the resemblance is more than superficial: physical principles governing emulsion stability also control lipid droplet nucleation and g...
journal_title:Developmental cell
pub_type: 评论,杂志文章,评审
doi:10.1016/j.devcel.2017.06.001
更新日期:2017-06-19 00:00:00
abstract::The kinase Plk1 plays multiple roles in regulating mitotic progression, including stabilization of spindle poles, but its substrates are largely unknown. A new study by Yamamoto and coworkers has identified a centrosomal protein, Kizuna (Kiz), as a mitotic substrate of Plk1 (Oshimori et al., 2006). Phosphorylation of ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2006.09.012
更新日期:2006-10-01 00:00:00
abstract::IRE1α, the most conserved transducer of the unfolded protein response, plays critical roles in many biological processes and cell fate decisions. Reporting in Science, Upton et al. (2012) broadened our understanding of IRE1α as a cell-death executioner, showing that upon ER stress, IRE1α degrades microRNAs to promote ...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2012.10.025
更新日期:2012-11-13 00:00:00
abstract::In vertebrate embryos, retinoic acid (RA) synthesized in the mesoderm by Raldh2 emanates to the hindbrain neuroepithelium, where it induces anteroposterior (AP)-restricted Hox expression patterns and rhombomere segmentation. However, how appropriate spatiotemporal RA activity is generated in the hindbrain is poorly un...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.03.011
更新日期:2011-04-19 00:00:00
abstract::Small GTPase Cdc42 triggers polarity establishment in budding yeast. In this issue of Developmental Cell, Okada et al. (2013) combine in silico modeling and cell biology to show that Cdc42, septins, and the exocytosis pathway are integrated in a feedback system to define and insulate the site of polarity in the membra...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2013.07.004
更新日期:2013-07-29 00:00:00
abstract::Reactive oxygen species (ROS) such as hydrogen peroxide are generated at wound sites and act as long-range signals in wound healing. The roles of other ROS in wound repair are little explored. Here, we reveal a cytoprotective role for mitochondrial ROS (mtROS) in Caenorhabditis elegans skin wound healing. We show that...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2014.08.002
更新日期:2014-10-13 00:00:00
abstract::Myosin phosphatase-targeting subunit 1 (MYPT1) binds to the catalytic subunit of protein phosphatase 1 (PP1C). This binding is believed to target PP1C to specific substrates including myosin II, thus controlling cellular contractility. Surprisingly, we found that during mitosis, mammalian MYPT1 binds to polo-like kina...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2008.02.013
更新日期:2008-05-01 00:00:00
abstract::Branching morphogenesis is a key process in the formation of vascular networks. To date, little is known regarding the molecular events regulating this process. We investigated the involvement of synectin in this process. In zebrafish embryos, synectin knockdown resulted in a hypoplastic dorsal aorta and hypobranched,...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2006.03.012
更新日期:2006-06-01 00:00:00
abstract::In the field of breast biology, there is a growing appreciation for the "gatekeeping function" of basal cells during development and disease processes yet mechanisms regulating the generation of these cells are poorly understood. Here, we report that the proliferation of basal cells is controlled by SLIT/ROBO1 signali...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.05.012
更新日期:2011-06-14 00:00:00
abstract::Wnt/β-catenin signaling plays critical roles during embryogenesis, tissue homeostasis, and regeneration. How Wnt-receptor complex activity is regulated is not yet fully understood. Here, we identify the Ly6 family protein LY6/PLAUR domain-containing 6 (Lypd6) as a positive feedback regulator of Wnt/β-catenin signaling...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2013.07.020
更新日期:2013-08-26 00:00:00
abstract::Exponential increase of cell numbers in early embryos requires large amounts of DNA precursors (deoxyribonucleoside triphosphates (dNTPs)). Little is understood about how embryos satisfy this demand. We examined dNTP metabolism in the early Drosophila embryo, in which gastrulation is preceded by 13 sequential nuclear ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2017.06.013
更新日期:2017-08-07 00:00:00
abstract::Reporting in Nature, Sanders et al. (2013) implicate filopodial projections in Sonic hedgehog (Shh) patterning of the limb. Actin-based filopodia transport Shh from producing cells, while filopodia of responding cells bear Cdon and Boc: coreceptors in the Shh pathway. These findings suggest a new mechanism of ligand m...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2013.05.008
更新日期:2013-05-28 00:00:00
abstract::The dorsoventral axis of the Drosophila embryo is patterned by a gradient of bone morphogenetic protein (BMP) ligands. In a process requiring at least three additional extracellular proteins, a broad domain of weak signaling forms and then abruptly sharpens into a narrow dorsal midline peak. Using experimental and com...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2005.04.009
更新日期:2005-06-01 00:00:00