Protein phosphatase 4 mediates localization of the Miranda complex during Drosophila neuroblast asymmetric divisions.

Abstract:

:Asymmetric localization of cell fate determinants is a crucial step in neuroblast asymmetric divisions. Whereas several protein kinases have been shown to mediate this process, no protein phosphatase has so far been implicated. In a clonal screen of larval neuroblasts we identified the evolutionarily conserved Protein Phosphatase 4 (PP4) regulatory subunit PP4R3/Falafel (Flfl) as a key mediator specific for the localization of Miranda (Mira) and associated cell fate determinants during both interphase and mitosis. Flfl is predominantly nuclear during interphase/prophase and cytoplasmic after nuclear envelope breakdown. Analyses of nuclear excluded as well as membrane targeted versions of the protein suggest that the asymmetric cortical localization of Mira and its associated proteins during mitosis depends on cytoplasmic/membrane-associated Flfl, whereas nuclear Flfl is required to exclude the cell fate determinant Prospero (Pros), and consequently Mira, from the nucleus during interphase/prophase. Attenuating the function of either the catalytic subunit of PP4 (PP4C; Pp4-19C in Drosophila) or of another regulatory subunit, PP4R2 (PPP4R2r in Drosophila), leads to similar defects in the localization of Mira and associated proteins. Flfl is capable of directly interacting with Mira, and genetic analyses indicate that flfl acts in parallel to or downstream from the tumor suppressor lethal (2) giant larvae (lgl). Our findings suggest that Flfl may target PP4 to the MIra protein complex to facilitate dephosphorylation step(s) crucial for its cortical association/asymmetric localization.

journal_name

Genes Dev

journal_title

Genes & development

authors

Sousa-Nunes R,Chia W,Somers WG

doi

10.1101/gad.1723609

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

359-72

issue

3

eissn

0890-9369

issn

1549-5477

pii

23/3/359

journal_volume

23

pub_type

杂志文章
  • The regulation of empty spiracles by Abdominal-B mediates an abdominal segment identity function.

    abstract::The empty spiracles (ems) homeo box gene is required for the development of the Drosophila larval filzkörper, which are structural specializations of the eighth abdominal segment. Filzkörper development is also dependent on the function of the homeotic selector gene Abdominal-B (Abd-B). Here, we show that ems is a dow...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.7.2.229

    authors: Jones B,McGinnis W

    更新日期:1993-02-01 00:00:00

  • Caudal, a key developmental regulator, is a DPE-specific transcriptional factor.

    abstract::The regulation of gene transcription is critical for the proper development and growth of an organism. The transcription of protein-coding genes initiates at the RNA polymerase II core promoter, which is a diverse module that can be controlled by many different elements such as the TATA box and downstream core promote...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1698108

    authors: Juven-Gershon T,Hsu JY,Kadonaga JT

    更新日期:2008-10-15 00:00:00

  • Nuclear receptor ERR alpha and coactivator PGC-1 beta are effectors of IFN-gamma-induced host defense.

    abstract::Macrophage activation by the proinflammatory cytokine interferon-gamma (IFN-gamma) is a critical component of the host innate response to bacterial pathogenesis. However, the precise nature of the IFN-gamma-induced activation pathway is not known. Here we show using genome-wide expression and chromatin-binding profili...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1553007

    authors: Sonoda J,Laganière J,Mehl IR,Barish GD,Chong LW,Li X,Scheffler IE,Mock DC,Bataille AR,Robert F,Lee CH,Giguère V,Evans RM

    更新日期:2007-08-01 00:00:00

  • Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase.

    abstract::SET8 (also known as PR-SET7) is a histone H4-Lys-20-specific methyltransferase that is implicated in cell-cycle-dependent transcriptional silencing and mitotic regulation in metazoans. Herein we report the crystal structure of human SET8 (hSET8) bound to a histone H4 peptide bearing Lys-20 and the product cofactor S-a...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1318405

    authors: Couture JF,Collazo E,Brunzelle JS,Trievel RC

    更新日期:2005-06-15 00:00:00

  • Human Rif1, ortholog of a yeast telomeric protein, is regulated by ATM and 53BP1 and functions in the S-phase checkpoint.

    abstract::We report on the function of the human ortholog of Saccharomyces cerevisiae Rif1 (Rap1-interacting factor 1). Yeast Rif1 associates with telomeres and regulates their length. In contrast, human Rif1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in AL...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1216004

    authors: Silverman J,Takai H,Buonomo SB,Eisenhaber F,de Lange T

    更新日期:2004-09-01 00:00:00

  • DNA damage activates p53 through a phosphorylation-acetylation cascade.

    abstract::Activation of p53-mediated transcription is a critical cellular response to DNA damage. p53 stability and site-specific DNA-binding activity and, therefore, transcriptional activity, are modulated by post-translational modifications including phosphorylation and acetylation. Here we show that p53 is acetylated in vitr...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.18.2831

    authors: Sakaguchi K,Herrera JE,Saito S,Miki T,Bustin M,Vassilev A,Anderson CW,Appella E

    更新日期:1998-09-15 00:00:00

  • A unified allosteric/torpedo mechanism for transcriptional termination on human protein-coding genes.

    abstract::The allosteric and torpedo models have been used for 30 yr to explain how transcription terminates on protein-coding genes. The former invokes termination via conformational changes in the transcription complex and the latter proposes that degradation of the downstream product of poly(A) signal (PAS) processing is imp...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.332833.119

    authors: Eaton JD,Francis L,Davidson L,West S

    更新日期:2020-01-01 00:00:00

  • Maternal Eed knockout causes loss of H3K27me3 imprinting and random X inactivation in the extraembryonic cells.

    abstract::Genomic imprinting is essential for mammalian development. Recent studies have revealed that maternal histone H3 Lys27 trimethylation (H3K27me3) can mediate DNA methylation-independent genomic imprinting. However, the regulatory mechanisms and functions of this new imprinting mechanism are largely unknown. Here we dem...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.318675.118

    authors: Inoue A,Chen Z,Yin Q,Zhang Y

    更新日期:2018-12-01 00:00:00

  • Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53.

    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

    authors: Howes KA,Ransom N,Papermaster DS,Lasudry JG,Albert DM,Windle JJ

    更新日期:1994-06-01 00:00:00

  • Hypersensitivity to DNA damage leads to increased apoptosis during early mouse development.

    abstract::Gastrulation in mice is associated with the start of extreme proliferation and differentiation. The potential cost to the embryo of a very rapid proliferation rate is a high production of damaged cells. We demonstrate a novel surveillance mechanism for the elimination of cells damaged by ionizing radiation during mous...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:

    authors: Heyer BS,MacAuley A,Behrendtsen O,Werb Z

    更新日期:2000-08-15 00:00:00

  • Cap-independent translation of encephalomyocarditis virus RNA: structural elements of the internal ribosomal entry site and involvement of a cellular 57-kD RNA-binding protein.

    abstract::Translation of encephalomyocarditis virus (EMCV) mRNA occurs by ribosomal internal entry into the 5'-nontranslated region (5' NTR) rather than by ribosomal scanning. The internal ribosomal entry site (IRES) in the EMCV 5' NTR was determined by in vitro translation with RNAs that were generated by in vitro transcriptio...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.4.9.1560

    authors: Jang SK,Wimmer E

    更新日期:1990-09-01 00:00:00

  • APC sets the Wnt tone necessary for cerebral cortical progenitor development.

    abstract::Adenomatous polyposis coli (APC) regulates the activity of β-catenin, an integral component of Wnt signaling. However, the selective role of the APC-β-catenin pathway in cerebral cortical development is unknown. Here we genetically dissected the relative contributions of APC-regulated β-catenin signaling in cortical p...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.302679.117

    authors: Nakagawa N,Li J,Yabuno-Nakagawa K,Eom TY,Cowles M,Mapp T,Taylor R,Anton ES

    更新日期:2017-08-15 00:00:00

  • miR760 regulates ATXN1 levels via interaction with its 5' untranslated region.

    abstract::Identifying modifiers of dosage-sensitive genes involved in neurodegenerative disorders is imperative to discover novel genetic risk factors and potential therapeutic entry points. In this study, we focus on Ataxin-1 (ATXN1), a dosage-sensitive gene involved in the neurodegenerative disease spinocerebellar ataxia type...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.339317.120

    authors: Nitschke L,Tewari A,Coffin SL,Xhako E,Pang K,Gennarino VA,Johnson JL,Blanco FA,Liu Z,Zoghbi HY

    更新日期:2020-09-01 00:00:00

  • Hat2p recognizes the histone H3 tail to specify the acetylation of the newly synthesized H3/H4 heterodimer by the Hat1p/Hat2p complex.

    abstract::Post-translational modifications of histones are significant regulators of replication, transcription, and DNA repair. Particularly, newly synthesized histone H4 in H3/H4 heterodimers becomes acetylated on N-terminal lysine residues prior to its incorporation into chromatin. Previous studies have established that the ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.240531.114

    authors: Li Y,Zhang L,Liu T,Chai C,Fang Q,Wu H,Agudelo Garcia PA,Han Z,Zong S,Yu Y,Zhang X,Parthun MR,Chai J,Xu RM,Yang M

    更新日期:2014-06-01 00:00:00

  • Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins.

    abstract::The Rho family of small GTPases are critical elements involved in the regulation of signal transduction cascades from extracellular stimuli to the cell nucleus, including the JNK/SAPK signaling pathway, the c-fos serum response factor, and the p70 S6 kinase. Here we report a novel signaling pathway activated by the Rh...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.11.4.463

    authors: Perona R,Montaner S,Saniger L,Sánchez-Pérez I,Bravo R,Lacal JC

    更新日期:1997-02-15 00:00:00

  • A zinc-binding site in the largest subunit of DNA-dependent RNA polymerase is involved in enzyme assembly.

    abstract::All multisubunit DNA-dependent RNA polymerases (RNAP) are zinc metalloenzymes, and at least two zinc atoms are present per enzyme molecule. RNAP residues involved in zinc binding and the functional role of zinc ions in the transcription mechanism or RNAP structure are unknown. Here, we locate four cysteine residues in...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.13.18.2439

    authors: Markov D,Naryshkina T,Mustaev A,Severinov K

    更新日期:1999-09-15 00:00:00

  • CBL family E3 ubiquitin ligases control JAK2 ubiquitination and stability in hematopoietic stem cells and myeloid malignancies.

    abstract::Janus kinase 2 (JAK2) is a central kinase in hematopoietic stem/progenitor cells (HSPCs), and its uncontrolled activation is a prominent oncogenic driver of hematopoietic neoplasms. However, molecular mechanisms underlying the regulation of JAK2 have remained elusive. Here we report that the Casitas B-cell lymphoma (C...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.297135.117

    authors: Lv K,Jiang J,Donaghy R,Riling CR,Cheng Y,Chandra V,Rozenova K,An W,Mohapatra BC,Goetz BT,Pillai V,Han X,Todd EA,Jeschke GR,Langdon WY,Kumar S,Hexner EO,Band H,Tong W

    更新日期:2017-05-15 00:00:00

  • Cooperating oncogenes converge to regulate cyclin/cdk complexes.

    abstract::The cooperation of oncogenes in the transformation of primary rat Schwann cells is a strikingly synergistic process. We have explored the molecular mechanisms involved. Activation of an inducible Raf kinase results in morphologically transformed cells that are arrested in G1 via the induction of p21(CiP1) and subseque...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.11.5.663

    authors: Lloyd AC,Obermüller F,Staddon S,Barth CF,McMahon M,Land H

    更新日期:1997-03-01 00:00:00

  • 3'-end formation of mouse pre-rRNA involves both transcription termination and a specific processing reaction.

    abstract::We have studied the sequence requirements for 3'-end formation of rDNA transcripts in a cell-free system and show that the generation of correct ends of mouse pre-rRNA is brought about by a two-step process that involves a bona fide termination reaction, followed by a specific trimming of the primary transcript by 10 ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.3.2.224

    authors: Kuhn A,Grummt I

    更新日期:1989-02-01 00:00:00

  • Genome-wide chromatin footprinting reveals changes in replication origin architecture induced by pre-RC assembly.

    abstract::Start sites of DNA replication are marked by the origin recognition complex (ORC), which coordinates Mcm2-7 helicase loading to form the prereplicative complex (pre-RC). Although pre-RC assembly is well characterized in vitro, the process is poorly understood within the local chromatin environment surrounding replicat...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.247924.114

    authors: Belsky JA,MacAlpine HK,Lubelsky Y,Hartemink AJ,MacAlpine DM

    更新日期:2015-01-15 00:00:00

  • Dimerization specificity of myogenic helix-loop-helix DNA-binding factors directed by nonconserved hydrophilic residues.

    abstract::The myogenic regulatory factor MyoD dimerizes with other positive and negative regulatory factors through a conserved region called the helix-loop-helix (HLH) domain. Using a non-DNA-binding MyoD mutant with a normal HLH domain as a dimerization competitor in gel mobility shift assays in conjunction with various MyoD ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.7.12a.2456

    authors: Shirakata M,Friedman FK,Wei Q,Paterson BM

    更新日期:1993-12-01 00:00:00

  • Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses.

    abstract::Placental development is profoundly influenced by oxygen (O(2)) tension. Human cytotrophoblasts proliferate in vitro under low O(2) conditions but differentiate at higher O(2) levels, mimicking the developmental transition they undergo as they invade the placental bed to establish the maternal-fetal circulation in viv...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.853700

    authors: Adelman DM,Gertsenstein M,Nagy A,Simon MC,Maltepe E

    更新日期:2000-12-15 00:00:00

  • Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.

    abstract::The amino-terminal histone tails are subject to covalent post-translational modifications such as acetylation, methylation, and phosphorylation. In the histone code hypothesis, these exposed and unstructured histone tails are accessible to a repertoire of regulatory factors that specifically recognize the various modi...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.1001502

    authors: Ng HH,Feng Q,Wang H,Erdjument-Bromage H,Tempst P,Zhang Y,Struhl K

    更新日期:2002-06-15 00:00:00

  • A TIN2 dyskeratosis congenita mutation causes telomerase-independent telomere shortening in mice.

    abstract::The progressive bone marrow failure syndrome dyskeratosis congenita (DC) is often caused by mutations in telomerase or the factors involved in telomerase biogenesis and trafficking. However, a subset of DC patients is heterozygous for mutations in the shelterin component TIN2. To determine how the TIN2-DC mutations af...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.233395.113

    authors: Frescas D,de Lange T

    更新日期:2014-01-15 00:00:00

  • Cotranscriptional recruitment of the dosage compensation complex to X-linked target genes.

    abstract::Dosage compensation is a process required to balance the expression of X-linked genes between males and females. In Drosophila this is achieved by targeting the dosage compensation complex or the male-specific lethal (MSL) complex to the male X chromosome. In order to study the mechanism of targeting, we have studied ...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.430807

    authors: Kind J,Akhtar A

    更新日期:2007-08-15 00:00:00

  • STAU1 binding 3' UTR IRAlus complements nuclear retention to protect cells from PKR-mediated translational shutdown.

    abstract::For a number of human genes that encode transcripts containing inverted repeat Alu elements (IRAlus) within their 3' untranslated region (UTR), product mRNA is efficiently exported to the cytoplasm when the IRAlus, which mediate nuclear retention, are removed by alternative polyadenylation. Here we report a new mechan...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.220962.113

    authors: Elbarbary RA,Li W,Tian B,Maquat LE

    更新日期:2013-07-01 00:00:00

  • Neuron type-specific miRNA represses two broadly expressed genes to modulate an avoidance behavior in C. elegans.

    abstract::Two broad gene classes are distinguished within multicellular organisms: cell type-specific genes, which confer particular cellular properties, and ubiquitous genes that support general cellular functions. However, certain so-called ubiquitous genes show functionally relevant cell type-specific repression. How such re...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.287904.116

    authors: Drexel T,Mahofsky K,Latham R,Zimmer M,Cochella L

    更新日期:2016-09-15 00:00:00

  • RAG-1 mutations that affect the target specificity of V(D)j recombination: a possible direct role of RAG-1 in site recognition.

    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

    authors: Sadofsky MJ,Hesse JE,van Gent DC,Gellert M

    更新日期:1995-09-01 00:00:00

  • GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2.

    abstract::Mammalian cells possess two amino acid-sensing kinases: general control nonderepressible 2 (GCN2) and mechanistic target of rapamycin complex 1 (mTORC1). Their combined effects orchestrate cellular adaptation to amino acid levels, but how their activities are coordinated remains poorly understood. Here, we demonstrate...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.269324.115

    authors: Ye J,Palm W,Peng M,King B,Lindsten T,Li MO,Koumenis C,Thompson CB

    更新日期:2015-11-15 00:00:00

  • Smad proteins act in combination with synergistic and antagonistic regulators to target Dpp responses to the Drosophila mesoderm.

    abstract::Dorsal mesoderm induction in arthropods and ventral mesoderm induction in vertebrates are closely related processes that involve signals of the BMP family. In Drosophila, induction of visceral mesoderm, dorsal muscles, and the heart by Dpp is, at least in part, effected through the transcriptional activation and funct...

    journal_title:Genes & development

    pub_type: 杂志文章

    doi:10.1101/gad.12.15.2354

    authors: Xu X,Yin Z,Hudson JB,Ferguson EL,Frasch M

    更新日期:1998-08-01 00:00:00