scholarly journals The ETS domain transcriptional repressor Anterior open inhibits MAP kinase and Wingless signaling to couple tracheal cell fate with branch identity

Development ◽  
2013 ◽  
Vol 140 (6) ◽  
pp. 1240-1249 ◽  
Author(s):  
S. Caviglia ◽  
S. Luschnig
Keyword(s):  
Map Kinase ◽  
Cell Fate ◽  
Transcriptional Repressor ◽  
Tracheal Cell ◽  
Wingless Signaling ◽  
Ets Domain

scholarly journals Spitz and Wingless, emanating from distinct borders, cooperate to establish cell fate across the Engrailed domain in the Drosophila epidermis

Development ◽  
1997 ◽  
Vol 124 (23) ◽  
pp. 4837-4845 ◽  
Author(s):  
L. O'Keefe ◽  
S.T. Dougan ◽  
L. Gabay ◽  
E. Raz ◽  
B.Z. Shilo ◽  
...  
Keyword(s):  
Map Kinase ◽  
Cell Fate ◽  
Egf Receptor ◽  
Cell Types ◽  
Cell Type ◽  
Gene Encoding ◽  
Relative Level ◽  
Ets Domain ◽  
Map Kinase Pathway ◽  
Kinase Pathway

A key step in development is the establishment of cell type diversity across a cellular field. Segmental patterning within the Drosophila embryonic epidermis is one paradigm for this process. At each parasegment boundary, cells expressing the Wnt family member Wingless confront cells expressing the homeoprotein Engrailed. The Engrailed-expressing cells normally differentiate as one of two alternative cell types. In investigating the generation of this cell type diversity among the 2-cell-wide Engrailed stripe, we previously showed that Wingless, expressed just anterior to the Engrailed cells, is essential for the specification of anterior Engrailed cell fate. In a screen for additional mutations affecting Engrailed cell fate, we identified anterior open/yan, a gene encoding an inhibitory ETS-domain transcription factor that is negatively regulated by the Rasl-MAP kinase signaling cascade. We find that Anterior Open must be inactivated for posterior Engrailed cells to adopt their correct fate. This is achieved by the EGF receptor (DER), which is required autonomously in the Engrailed cells to trigger the Ras1-MAP kinase pathway. Localized activation of DER is accomplished by restricted processing of the activating ligand, Spitz. Processing is confined to the cell row posterior to the Engrailed domain by the restricted expression of Rhomboid. These cells also express the inhibitory ligand Argos, which attenuates the activation of DER in cell rows more distant from the ligand source. Thus, distinct signals flank each border of the Engrailed domain, as Wingless is produced anteriorly and Spitz posteriorly. Since we also show that En cells have the capacity to respond to either Wingless or Spitz, these cells must choose their fate depending on the relative level of activation of the two pathways.

scholarly journals Ral Signals through a MAP4 Kinase-p38 MAP Kinase Cascade in C. elegans Cell Fate Patterning

Cell Reports ◽  
2018 ◽  
Vol 24 (10) ◽  
pp. 2669-2681.e5 ◽  
Author(s):  
Hanna Shin ◽  
Rebecca E.W. Kaplan ◽  
Tam Duong ◽  
Razan Fakieh ◽  
David J. Reiner
Keyword(s):  
Map Kinase ◽  
Cell Fate ◽  
P38 Map Kinase ◽  
C Elegans ◽  
Map Kinase Cascade ◽  
Kinase Cascade

The Ets Transcription Factor, GABP, Is Required by Myeloid Progenitors for Normal Myeloid Differentiation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 256-256
Author(s):  
Zhongfa Yang ◽  
Karen Drumea ◽  
Junling Wang ◽  
James Cormier ◽  
Alan G. Rosmarin
Keyword(s):  
Cell Cycle ◽  
Bone Marrow ◽  
Transcription Factor ◽  
Progenitor Cells ◽  
Peripheral Blood ◽  
Transcriptional Repressor ◽  
Myeloid Cell ◽  
Myeloid Differentiation ◽  
Ets Domain

Abstract Abstract 256 GABP transcription factor regulates genes that are required for innate immunity. GABP is an obligate tetrameric protein complex that contains two molecules of GABPa, which binds to DNA through its ets domain, and two molecules of GABPb, which contains a transcription activation domain. GABP is an essential component of a multiprotein enhanceosome that is required for retinoic acid-dependent myeloid gene transcription. Disruption in mouse embryo fibroblasts of Gabpa, the mouse gene that encodes mouse Gabpa, causes profound cell cycle arrest at the G1-S boundary, due to reduced expression of DNA Polymerase a and Thymidylate Synthase, which are required for DNA synthesis, and of Skp2, a ubiquitin ligase that controls degradation of the cyclin-dependent kinase inhibitors (CDKIs), p21 and p27. Thus, GABP is a key regulator of the cell cycle. In order to define the role of GABP in myeloid differentiation, we generated mice in which exons that encode the Gabpa ets domain are flanked by loxP recombination sites, and bred these floxed mice to mice that bear the Mx1-Cre transgene. Their progeny were treated with pI-C and Gabpa was efficiently deleted in hematopoietic cells of these Gabpa−/− mice. As controls for all experiments, mice that bear Mx1-Cre but which lack the floxed Gabpa allele were also injected with pI-C. Within days, the peripheral blood white blood cell count fell in the Gabpa−/− mice compared to the controls; half of the Gabpa−/− mice died within two weeks. Gabpa−/− mice exhibited a striking loss of Gr1+, CD11b+ cells in the peripheral blood, spleen, and bone marrow. Myeloid cells of Gabpa−/− mice were immature, morphologically dysplastic, and demonstrated aberrant patterns of myeloid gene expression. Bone marrow from Gabpa−/− mice formed reduced numbers of in vitro myeloid colonies in the presence of G-CSF, M-CSF, or GM-CSF; cells isolated from in vitro colonies from Gabpa−/− mice exhibited a strong bias toward macrophage-like morphology. Multicolor flow cytometry revealed a loss of granulocyte-monocyte committed progenitor cells (GMPs) in the bone marrow of Gabpa−/− mice, and these progenitors expressed aberrant patterns of key transcription factors. Especially notable in Gabpa−/− GMPs was reduced expression of Gfi-1, a transcriptional repressor that is mutated in some congenital neutropenic syndromes, and whose genetic disruption causes abnormalities in granulocyte development. We used chromatin immunoprecipitation (ChIP) to identify ets sites in the Gfi-1 promoter that are bound by GABP in vivo. We conclude that GABP is required for proliferation or survival of committed myeloid progenitor cells and for normal maturation of granulocytes. We hypothesize that defects in myeloid cell proliferation and differentiation associated with Gabpa disruption are caused, at least in part, by its regulation of the Gfi-1 transcriptional repressor. Furthermore, we propose that the regulation of Gfi-1 by GABP constitutes a key regulatory pathway in myeloid cell development. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MAP Kinase Signaling Antagonizes PAR-1 Function During Polarization of the Early Caenorhabditis elegans Embryo

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 965-977 ◽  
Author(s):  
Annina C. Spilker ◽  
Alexia Rabilotta ◽  
Caroline Zbinden ◽  
Jean-Claude Labbé ◽  
Monica Gotta
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Map Kinase ◽  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Asymmetric Distribution ◽  
Kinase Signaling ◽  
C Elegans ◽  
Link Type ◽  
Map Kinase Signaling

PAR proteins (partitioning defective) are major regulators of cell polarity and asymmetric cell division. One of the par genes, par-1, encodes a Ser/Thr kinase that is conserved from yeast to mammals. In Caenorhabditis elegans, par-1 governs asymmetric cell division by ensuring the polar distribution of cell fate determinants. However the precise mechanisms by which PAR-1 regulates asymmetric cell division in C. elegans remain to be elucidated. We performed a genomewide RNAi screen and identified six genes that specifically suppress the embryonic lethal phenotype associated with mutations in par-1. One of these suppressors is mpk-1, the C. elegans homolog of the conserved mitogen activated protein (MAP) kinase ERK. Loss of function of mpk-1 restored embryonic viability, asynchronous cell divisions, the asymmetric distribution of cell fate specification markers, and the distribution of PAR-1 protein in par-1 mutant embryos, indicating that this genetic interaction is functionally relevant for embryonic development. Furthermore, disrupting the function of other components of the MAPK signaling pathway resulted in suppression of par-1 embryonic lethality. Our data therefore indicates that MAP kinase signaling antagonizes PAR-1 signaling during early C. elegans embryonic polarization.

The ETS domain protein Pointed-P2 is a target of MAP kinase in the Sevenless signal transduction pathway

Nature ◽  
1994 ◽  
Vol 370 (6488) ◽  
pp. 386-389 ◽  
Author(s):  
Damian Brunner ◽  
Klaus Dücker ◽  
Nadja Oellers ◽  
Ernst Hafen ◽  
Henrike Scholzi ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Map Kinase ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Ets Domain ◽  
Domain Protein

scholarly journals FEV acts as a transcriptional repressor through its DNA-binding ETS domain and alanine-rich domain

Oncogene ◽  
2003 ◽  
Vol 22 (21) ◽  
pp. 3319-3329 ◽  
Author(s):  
Philippe Maurer ◽  
France T'Sas ◽  
Laurent Coutte ◽  
Nathalie Callens ◽  
Carmen Brenner ◽  
...  
Keyword(s):  
Dna Binding ◽  
Transcriptional Repressor ◽  
Rich Domain ◽  
Ets Domain

scholarly journals Deubiquitylating Enzyme UBP64 Controls Cell Fate through Stabilization of the Transcriptional Repressor Tramtrack

2007 ◽  
Vol 28 (5) ◽  
pp. 1606-1615 ◽  
Author(s):  
Prashanth Kumar Bajpe ◽  
Jan A. van der Knaap ◽  
Jeroen A. A. Demmers ◽  
Karel Bezstarosti ◽  
Andrew Bassett ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Substrate Specificity ◽  
Cell Fate ◽  
Transcriptional Repressor ◽  
Neuronal Cell ◽  
Mass Spectrometric ◽  
Signal Transduction Pathways ◽  
Cone Cells ◽  
Proteomics Approach ◽  
Scanning Mechanism

ABSTRACT Protein ubiquitylation plays a central role in multiple signal transduction pathways. However, the substrate specificity and potential developmental roles of deubiquitylating enzymes remain poorly understood. Here, we show that the Drosophila ubiquitin protease UBP64 controls cell fate in the developing eye. UBP64 represses neuronal cell fate but promotes the formation of nonneuronal cone cells. Using a proteomics approach, we identified the transcriptional repressor Tramtrack (TTK) as a primary UBP64 substrate. In common with TTK, reduced UBP64 levels lead to a loss of cone cells, supernumerary photoreceptors, and mechanosensory bristle cells. Previously, it was demonstrated that the blockade of neuronal cell fate was relieved by SINA-dependent ubiquitylation and degradation of TTK. We found that UBP64 counteracts SINA function by deubiquitylating TTK, leading to its stabilization and thereby promoting a nonneuronal cell fate. Mass spectrometric mapping revealed that SINA ubiquitylates multiple sites dispersed throughout TTK, which are duly deubiquitylated by UBP64. This observation suggests that both E3 SINA and UBP64 use a scanning mechanism to (de)ubiquitylate TTK. We conclude that the balance of TTK ubiquitylation by SINA and deubiquitylation by UBP64 constitutes a specific posttranslational switch controlling cell fate.

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