Abstract:
:The large GTPase Dynamin 2 (Dyn2) is markedly upregulated in pancreatic cancer, is a potent activator of metastatic migration, and is required for Rac1-mediated formation of lamellipodia. Here we demonstrate an unexpected mechanism of Dyn2 action in these contexts via direct binding to the Rac1 guanine nucleotide exchange factor (GEF) Vav1. Surprisingly, disruption of the Dyn2-Vav1 interaction targets Vav1 to the lysosome for degradation via an interaction with the cytoplasmic chaperone Hsc70, resulting in a dramatic reduction of Vav1 protein stability. Importantly, a specific mutation in Vav1 near its Dyn2-binding C-terminal Src homology 3 (SH3) domain prevents Hsc70 binding, resulting in a stabilization of Vav1 levels. Dyn2 binding regulates the interaction of Vav1 with Hsc70 to control the stability and subsequent activity of this oncogenic GEF. These findings elucidate how Dyn2 activates Rac1, lamellipod protrusion, and invasive cellular migration and provide insight into how this specific Vav is ectopically expressed in pancreatic tumors.
journal_name
Dev Celljournal_title
Developmental cellauthors
Razidlo GL,Wang Y,Chen J,Krueger EW,Billadeau DD,McNiven MAdoi
10.1016/j.devcel.2013.02.010subject
Has Abstractpub_date
2013-03-25 00:00:00pages
573-85issue
6eissn
1534-5807issn
1878-1551pii
S1534-5807(13)00122-6journal_volume
24pub_type
杂志文章abstract::It has recently been reported that a common side effect of translation-blocking morpholino antisense oligonucleotides is the induction of a set of innate immune response genes in Xenopus embryos and that splicing-blocking morpholinos lead to unexpected off-target mis-splicing events. Here, we present an analysis of al...
journal_title:Developmental cell
pub_type: 杂志文章,评审
doi:10.1016/j.devcel.2019.04.019
更新日期:2019-05-20 00:00:00
abstract::Vertebrate hematopoiesis first produces primitive (embryonic) lineages and ultimately generates the definitive (adult) blood. Whereas definitive hematopoiesis may produce many diverse blood types via a common multipotent progenitor, primitive hematopoiesis has been thought to produce only erythrocytes or macrophages v...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.04.007
更新日期:2009-05-01 00:00:00
abstract::The majority of excitatory synaptic transmission in the brain occurs at dendritic spines, which are actin-rich protrusions on the dendrites. The asymmetric nature of these structures suggests that proteins regulating cell polarity might be involved in their formation. Indeed, the polarity protein PAR-3 is required for...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.11.020
更新日期:2008-02-01 00:00:00
abstract::Pancreatic beta cells have been shown to be heterogeneous at multiple levels. However, spatially interrogating transcriptional heterogeneity in the intact tissue has been challenging. Here, we developed an optimized protocol for single-molecule transcript imaging in the intact pancreas and used it to identify a sub-po...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.11.001
更新日期:2019-01-07 00:00:00
abstract::Microglia are the primary immune cells in the brain. Under physiological conditions, they typically stay in a "resting" state, with ramified processes continuously extending to and retracting from surrounding neural tissues. Whether and how such highly dynamic resting microglia functionally interact with surrounding n...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2012.10.027
更新日期:2012-12-11 00:00:00
abstract::The identities of the ubiquitin-ligases active during myogenesis are largely unknown. Here we describe a RING-type E3 ligase complex specified by the adaptor protein, Ozz, a novel SOCS protein that is developmentally regulated and expressed exclusively in striated muscle. In mice, the absence of Ozz results in overt m...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(04)00020-6
更新日期:2004-02-01 00:00:00
abstract::Exposing cells to folding stress causes a subset of their proteins to misfold and accumulate in inclusion bodies (IBs). IB formation and clearance are both active processes, but little is known about their mechanism. To shed light on this issue, we performed a screen with over 4,000 fluorescently tagged yeast proteins...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.04.015
更新日期:2015-06-08 00:00:00
abstract::The Arf tumor suppressor is a key component of the p53 tumor surveillance pathway, and its expression is activated by abnormal proliferation signals. In a recent paper, Lees and coworkers investigate the regulation of Arf expression by E2Fs and demonstrate that in normal cells E2F3 is a pivotal repressor of Arf. ...
journal_title:Developmental cell
pub_type: 评论,杂志文章,评审
doi:10.1016/j.devcel.2004.05.012
更新日期:2004-06-01 00:00:00
abstract::Mbl is a bacterial actin homolog that controls cell morphogenesis in Bacillus subtilis. A functional GFP-Mbl fusion protein was used to examine the behavior of the helical cables formed by Mbl protein in live B. subtilis cells. The cables undergo dynamic changes during cell cycle progression. They are stable but not r...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(02)00403-3
更新日期:2003-01-01 00:00:00
abstract::Cell polarity plays a key role in the development of the central nervous system (CNS). Interestingly, disruption of cell polarity is seen in many cancers. ASPP2 is a haplo-insufficient tumor suppressor and an activator of the p53 family. In this study, we show that ASPP2 controls the polarity and proliferation of neur...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2010.06.003
更新日期:2010-07-20 00:00:00
abstract::Brassinosteroids (BRs) are essential hormones for plant growth and development. BRs regulate gene expression by inducing dephosphorylation of two key transcription factors, BZR1 and BZR2/BES1, through a signal transduction pathway that involves cell-surface receptors (BRI1 and BAK1) and a GSK3 kinase (BIN2). How BR-re...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.06.009
更新日期:2007-08-01 00:00:00
abstract::The viral genomes of alpha- and gamma-retroviruses follow an outbound route through the cytoplasm before assembling with the budding particle at the plasma membrane. We show here that murine leukemia virus (MLV) RNAs are transported on lysosomes and transferrin-positive endosomes. Transport on transferrin-positive ves...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00188-6
更新日期:2003-07-01 00:00:00
abstract::Germ cells, the cells that give rise to sperm and egg, maintain the potential to recreate all cell types in a new individual. This wide developmental potential, or totipotency, is manifested in unusual tumors called teratomas, in which germ cells undergo somatic differentiation. Although recent studies have implicated...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.08.003
更新日期:2009-09-01 00:00:00
abstract::The Decapentaplegic and Notch signaling pathways are thought to direct regional specification in the Drosophila eye-antennal epithelium by controlling the expression of selector genes for the eye (Eyeless/Pax6, Eyes absent) and/or antenna (Distal-less). Here, we investigate the function of these signaling pathways in ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00243-0
更新日期:2003-09-01 00:00:00
abstract::The biogenesis of lipid droplets (LDs) and the development of adipocytes are two key aspects of mammalian fat storage. SEIPIN, an integral membrane protein of the endoplasmic reticulum (ER), plays a critical role in both LD formation and adipogenesis. The molecular function of SEIPIN, however, has yet to be elucidated...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.09.010
更新日期:2018-10-22 00:00:00
abstract::Odorant receptors (ORs) in the olfactory epithelium bind to volatile small molecules leading to the perception of smell. ORs are expressed in many tissues but their functions are largely unknown. We show multiple ORs display distinct mRNA expression patterns during myogenesis in vitro and muscle regeneration in vivo. ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.09.004
更新日期:2009-11-01 00:00:00
abstract::Adult neurogenic niches are present in both vertebrates and invertebrates. Where do stem cells populating these niches originate, and what are the mechanisms maintaining their self-renewal? In this issue of Developmental Cell, Benton et al. (2014) show that in crayfish, hemolymph-derived cells enter a neurogenic niche...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2014.07.024
更新日期:2014-08-11 00:00:00
abstract::A remarkable feature of development is its reproducibility, the ability to correct embryo-to-embryo variations and instruct precise patterning. In Drosophila, embryonic patterning along the anterior-posterior axis is controlled by the morphogen gradient Bicoid (Bcd). In this article, we describe quantitative studies o...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2008.09.004
更新日期:2008-10-01 00:00:00
abstract::Mutations in Pkd1, encoding polycystin-1 (PC1), cause autosomal-dominant polycystic kidney disease (ADPKD). We show that the carboxy-terminal tail (CTT) of PC1 is released by γ-secretase-mediated cleavage and regulates the Wnt and CHOP pathways by binding the transcription factors TCF and CHOP, disrupting their intera...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2011.10.028
更新日期:2012-01-17 00:00:00
abstract::The gastrulating vertebrate embryo develops three germlayers: ectoderm, mesoderm, and endoderm. Zebrafish endoderm differentiation starts with the activation of sox17 by casanova (cas). We report that spg (pou2/Oct4) is essential for endoderm formation. Embryos devoid of maternal and zygotic spg function (MZspg) lack ...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/s1534-5807(03)00396-4
更新日期:2004-01-01 00:00:00
abstract::By functioning as an enzyme cofactor, hemoglobin component, and gene regulator, heme is vital for life. One mode of heme-regulated transcription involves amplifying the activity of GATA-1, a key determinant of erythrocyte differentiation. To discover biological consequences of the metal cofactor-transcription factor m...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2018.07.022
更新日期:2018-09-10 00:00:00
abstract::Enhancers are the primary determinants of cell identity, but the regulatory components controlling enhancer turnover during lineage commitment remain largely unknown. Here we compare the enhancer landscape, transcriptional factor occupancy, and transcriptomic changes in human fetal and adult hematopoietic stem/progeni...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.12.014
更新日期:2016-01-11 00:00:00
abstract::We developed a comprehensive dataset that samples the mouse transcriptome every 6 hr, from gastrulation through organogenesis. We observe an abrupt increase in overall transcript diversity at the onset of organogenesis (e8.0); the genes that comprise these changes are preferentially clustered along chromosome 7 and co...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2007.10.004
更新日期:2007-12-01 00:00:00
abstract::In response to cellular stress, mitochondria remodel their structure by organelle division and fusion. In this issue of Developmental Cell, Cooper et al. (2014) report that a nuclear protein, cyclin C, is recruited from nuclei to mitochondria upon oxidative stress and promotes mitochondrial division and apoptosis of t...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2014.01.010
更新日期:2014-01-27 00:00:00
abstract::Genome condensation during mitosis presents a chromatin landscape largely inaccessible to RNA polymerase II and most transcription factors. Caravaca et al. (2013) now report in Genes and Development that the pioneer transcription factor FOXA1 is retained at mitotic chromosomes, bookmarking the genome to enable gene ex...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2013.02.005
更新日期:2013-02-25 00:00:00
abstract::Spindle checkpoint silencing is crucial for cell-cycle progression, but mechanisms underlying this process remain mysterious. Two papers, one in this issue of Developmental Cell (Meadows et al., 2011) and one in Current Biology (Rosenberg et al., 2011), begin to show how phosphatase PP1-gamma connects chromosome-micro...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2011.05.017
更新日期:2011-06-14 00:00:00
abstract::RITS (RNA-induced initiation of transcriptional gene silencing complex) plays diverse roles in heterochromatin regulation: silencing transcription by recruitment of chromatin modifiers and destroying transcripts by RNAi. In a recent issue of Molecular Cell, Li et al. now show that the polymerization of Tas3, a compone...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2009.05.002
更新日期:2009-05-01 00:00:00
abstract::Pericytes are critical for cerebrovascular maturation and development of the blood-brain barrier (BBB), but their role in maintenance of the adult BBB, and how CNS pericytes differ from those of other tissues, is less well understood. We show that the forkhead transcription factor Foxf2 is specifically expressed in pe...
journal_title:Developmental cell
pub_type: 杂志文章
doi:10.1016/j.devcel.2015.05.008
更新日期:2015-07-06 00:00:00
abstract::Although it is well appreciated that autophagy begins with phagophore formation and expansion through lipid acquisition to become the autophagosome, this process remains poorly understood, with the source of autophagosome membrane controversial. Reporting recently in Nature, Hamasaki et al. (2013) suggest that the ER-...
journal_title:Developmental cell
pub_type: 评论,杂志文章
doi:10.1016/j.devcel.2013.04.004
更新日期:2013-04-29 00:00:00
abstract::T-box genes encode DNA binding transcription factors known to regulate a wide variety of developmental processes during embryogenesis and are present in the genomes of all multicellular animals. Indeed, alongside other more familiar families of developmental regulators such as Hox, Sox, and Pax, T-box genes constitute...
journal_title:Developmental cell
pub_type:
doi:10.1016/s1534-5807(02)00330-1
更新日期:2002-11-01 00:00:00