Abstract:
:To define the functional pathways regulating epithelial cell migration, we performed a genome-wide RNAi screen using 55,000 pooled lentiviral shRNAs targeting ∼11,000 genes, selecting for transduced cells with increased motility. A stringent validation protocol generated a set of 31 genes representing diverse pathways whose knockdown dramatically enhances cellular migration. Some of these pathways share features of epithelial-to-mesenchymal transition (EMT), and together they implicate key regulators of transcription, cellular signaling, and metabolism, as well as novel modulators of cellular trafficking, such as DLG5. In delineating downstream pathways mediating these migration phenotypes, we observed universal activation of ERKs and a profound dependence on their RSK effectors. Pharmacological inhibition of RSK dramatically suppresses epithelial cell migration induced by knockdown of all 31 genes, suggesting that convergence of diverse migratory pathways on this kinase may provide a therapeutic opportunity in disorders of cell migration, including cancer metastasis.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Smolen GA,Zhang J,Zubrowski MJ,Edelman EJ,Luo B,Yu M,Ng LW,Scherber CM,Schott BJ,Ramaswamy S,Irimia D,Root DE,Haber DAdoi
10.1101/gad.1989110subject
Has Abstractpub_date
2010-12-01 00:00:00pages
2654-65issue
23eissn
0890-9369issn
1549-5477pii
gad.1989110journal_volume
24pub_type
杂志文章abstract::The mouse Nedd5 gene encodes a 41.5-kD GTPase similar to the Saccharomyces and Drosophila septins essential for cytokinesis. Nedd5 accumulates near the contractile ring from anaphase through telophase, and finally condenses into the midbody. Microinjection of anti-Nedd5 antibody interferes with cytokinesis, giving ris...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.12.1535
更新日期:1997-06-15 00:00:00
abstract::The discovery of transcription factors (TFs) controlling pathways in health and disease is of paramount interest. We designed a widely applicable method, dubbed barcorded synthetic tandem repeat promoter screening (BC-STAR-PROM), to identify signal-activated TFs without any a priori knowledge about their properties. T...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.284828.116
更新日期:2016-08-15 00:00:00
abstract::To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slow...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.178962.111
更新日期:2011-12-01 00:00:00
abstract::The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center (GC) B and T cells and required for GC formation and antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.13.1953
更新日期:1998-07-01 00:00:00
abstract::The liver regenerates upon partial hepatectomy (PH) as terminally differentiated hepatocytes undergo a tremendous proliferative process. CREM gene expression is powerfully induced during liver regeneration. We show that cell proliferation is significantly reduced upon PH in CREM-/- mice. There is a reduction in DNA sy...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.23.3639
更新日期:1998-12-01 00:00:00
abstract::Lipids play crucial roles in many aspects of glial cell biology, affecting processes ranging from myelin membrane biosynthesis to axo-glial interactions. In order to study the role of lipid metabolism in myelinating glial cells, we specifically deleted in Schwann cells the Lpin1 gene, which encodes the Mg2+-dependent ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1638008
更新日期:2008-06-15 00:00:00
abstract::The Rad51 and Lim15 proteins of lily, which are homologs of the bacterial RecA protein, were found on chromosomes in various stages of meiotic prophase 1. The presence of both Rad51 and Lim15 proteins as discrete foci on leptotene and zygotene chromosomes and their colocalization suggest that meiotic recombination beg...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.8.925
更新日期:1995-04-15 00:00:00
abstract::The yeast SAGA (Spt-Ada-Gcn5-acetyltransferase) coactivator complex exerts functions in gene expression, including activator interaction, histone acetylation, histone deubiquitination, mRNA export, chromatin recognition, and regulation of the basal transcription machinery. These diverse functions involve distinct modu...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.184705.111
更新日期:2012-03-15 00:00:00
abstract::In Drosophila germ cells, PIWI-interacting RNAs (piRNAs) are amplified through a PIWI slicer-dependent feed-forward loop termed the ping-pong cycle, yielding secondary piRNAs. However, the detailed mechanism remains poorly understood, largely because an ex vivo model system amenable to biochemical analyses has not bee...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.283929.116
更新日期:2016-07-15 00:00:00
abstract::Class switch recombination (CSR) diversifies antibodies for productive immune responses while maintaining stability of the B-cell genome. Transcription at the immunoglobulin heavy chain (Igh) locus targets CSR-associated DNA damage and is promoted by the BRCT domain-containing PTIP (Pax transactivation domain-interact...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.268797.115
更新日期:2016-01-15 00:00:00
abstract::Mammalian histone gene transcription is increased approximately fivefold during the transition from the G1 phase to the S phase of the cell cycle. In this study, we present a detailed in vivo analysis of the human histone H2b promoter, which establishes that transcriptional regulation of this gene is mediated by a sub...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.2.1.32
更新日期:1988-01-01 00:00:00
abstract::Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a me...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.18.2266
更新日期:1995-09-15 00:00:00
abstract::The control of translation and mRNA degradation is an important part of the regulation of gene expression. It is now clear that small RNA molecules are common and effective modulators of gene expression in many eukaryotic cells. These small RNAs that control gene expression can be either endogenous or exogenous micro ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1399806
更新日期:2006-03-01 00:00:00
abstract::A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen-trans...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.11.1300
更新日期:1994-06-01 00:00:00
abstract::Subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs) are common brain lesions found in patients with tuberous sclerosis complex (TSC). These brain lesions present a mixed glioneuronal phenotype and have been hypothesized to originate from neural stem cells. However, this hypothesis has not been...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.16750211
更新日期:2011-08-01 00:00:00
abstract::Calcineurin, a conserved Ca(2+)/calmodulin-regulated protein phosphatase, plays a crucial role in Ca(2+) signaling in a wide variety of cell types. In Saccharomyces cerevisiae, calcineurin positively regulates transcription in response to stress by dephosphorylating the transcription factor Crz1p/Tcn1p. Dephosphorylat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.967602
更新日期:2002-03-01 00:00:00
abstract::We have shown that Wnt signals are necessary and sufficient for neural crest cells to adopt pigment cell fates. nacre, a zebrafish homolog of MITF, is required for pigment cell differentiation. We isolated a promoter region of nacre that contains Tcf/Lef binding sites, which can mediate Wnt responsiveness. This promot...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-01-15 00:00:00
abstract::Members of the metazoan nuclear receptor superfamily regulate gene expression programs in response to binding of cognate lipophilic ligands. Evolutionary studies using bioinformatics tools have concluded that lower eukaryotes, such as fungi, lack nuclear receptor homologs. Here we review recent discoveries suggesting ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1743009
更新日期:2009-02-15 00:00:00
abstract::Translation initiation factor 2 (eIF2) bound to GTP transfers the initiator methionyl tRNA to the 40S ribosomal subunit. The eIF5 stimulates GTP hydrolysis by the eIF2/GTP/Met-tRNA(i)(Met) ternary complex on base-pairing between Met-tRNA(i)(Met) and the start codon. The eIF2, eIF5, and eIF1 all have been implicated in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.831800
更新日期:2000-10-01 00:00:00
abstract::AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. It arose very early during eukaryotic evolution, and its ancestral role may have been in the response to starvation. Recent work shows that the kinase is activated by increases not only in AMP, but also in ADP....
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.17420111
更新日期:2011-09-15 00:00:00
abstract::The subdivision of the Drosophila body into distinct terminal and central domains depends on the torso (tor) protein, a putative receptor tyrosine kinase that is active at both ends of the early embryo. We show that the tor protein is uniformly expressed along the surface membrane of early embryos despite its localize...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.12b.2025
更新日期:1989-12-01 00:00:00
abstract::DNA replication remains unfinished in many Drosophila polyploid cells, which harbor disproportionately fewer copies of late-replicating chromosomal regions. By analyzing paired-end high-throughput sequence data from polytene larval salivary gland cells, we define 112 underreplicated (UR) euchromatic regions 60-480 kb ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.245811.114
更新日期:2014-08-15 00:00:00
abstract::Post-translational processes are essential for the generation and dynamics of mammalian circadian rhythms. In particular, phosphorylation of the key circadian protein PER2 precisely controls the period and phase of circadian oscillations. However, the mechanisms underlying that control are poorly understood. Here, we ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.512209
更新日期:2009-03-15 00:00:00
abstract::RNA polymerase II nascent transcripts are capped during pausing before elongation. Here we report that hSPT5, the human homolog of yeast elongation factor SPT5, interacts directly with the capping enzyme. hSPT5 stimulated capping enzyme guanylylation and mRNA capping by severalfold. Although RNA 5'-triphosphatase acti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.13.14.1774
更新日期:1999-07-15 00:00:00
abstract::The visual system is a powerful model for probing the development, connectivity, and function of neural circuits. Two genetically tractable species, mice and flies, are together providing a great deal of understanding of these processes. Current efforts focus on integrating knowledge gained from three cross-fostering ...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.248245.114
更新日期:2014-12-01 00:00:00
abstract::During development of the somatic macronucleus of Tetrahymena thermophila, the rDNA is excised from its germ-line chromosome, rearranged into a palindrome, and amplified to 10(4) copies. We have identified a cis-acting germ-line mutation, rmm11/6, that prevents amplification of the rDNA in all but approximately 1 in 1...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.1.84
更新日期:1994-01-01 00:00:00
abstract::The RAG-1 protein plays an essential role in V(D)j recombination, but its exact function has not yet been defined. Here we report that a particular mutation in RAG-1 affects recombination by altering the specificity of target sequence usage. Recombination mediated by wild-type RAG-1 is tolerant of a wide range of codi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.17.2193
更新日期:1995-09-01 00:00:00
abstract::Cell fates in the optic neuroepithelium are determined by the combinational action of homeotic transcription factors. One of these is Vax2, a homeodomain protein that ventralizes the vertebrate eye field by repressing transcription of the Pax6 gene. We find that Vax2 shuttles between the nucleus and cytoplasm as a fun...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1462706
更新日期:2006-10-15 00:00:00
abstract::The sigma(28) protein is a member of the bacterial sigma(70)-family of transcription factors that directs RNA polymerase to flagellar late (class 3) promoters. The sigma(28) protein is regulated in response to flagellar assembly by the anti-sigma(28) factor FlgM. FlgM inhibits sigma(28)-dependent transcription of gene...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.380406
更新日期:2006-08-15 00:00:00
abstract::Sequence analysis of an embryonic transcript of Drosophila predicts a tyrosine protein kinase-related gene. The prediction is based on several protein domains that are homologous to the functional domains of kinase-related oncogenes and several serine, threonine, and tyrosine protein kinases. For this reason, we named...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.8.862
更新日期:1987-10-01 00:00:00