Identification of a Midkine-associated gene expression profile in melanoma cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE131203 | GEO | 2020/10/15
REPOSITORIES: GEO
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Project description:Identification of a Midkine-associated gene expression profile in melanoma cells
| PRJNA542893 | ENA
Project description:The aim of this study is to understand the mechanisms of TDP-43 neurotoxicity. Here, we perform a RNA-Seq analysis in TDP-43 gain-of-fucntion (GOF) , TDP-43 loss-of-function and wild-type late pupae heads (73-90 hours APF) and perform TDP-43 GOF vs wild type and TDP-43 LOF vs wild-type differential expression analysis to show that both mechanisms presents defects in ecdysone receptor (ECR)-dependeint transcriptional program switching, and strongly deregulate expression from the neuronal microtubule associated protien Map205. RNA-seq was performed in two wild-type D.melanogaster biological replicates (Canton S, w1118 ), four biological replicates for TDP-43 (LOF) with two distinct genotypes (dTDP-43Δ142/Df(2R)106,dTDP-43Δ23/Δ142 ) and two TDP-43 GOF biological replicates (act5c>dTDP-43 ).
2013-01-22 | E-GEOD-42844 | biostudies-arrayexpress
Project description:NOTCH1 is a transmembrane receptor that initiates the Notch signaling pathway involved in embryonic development and maintenance of adult tissue homeostasis. The extracellular part of NOTCH1 is composed largely of EGF-like domains (EGFs) many of which can be O-fucosylated by protein O-fucosyltransferase 1 (POFUT1). O-fucosylation of NOTCH1 is necessary for its function. The Notch pathway is deregulated in many cancers, and alteration of POFUT1 has been reported in some cancers. Using the Biomuta and COSMIC databases, we selected 9 NOTCH1 variants that could cause a change in O-fucosylation of key EGFs. Cell-based N1 signaling assays, Notch ligand-binding assays and cell surface N1 analysis were used to determine the effect of each mutation on Notch activation. Then mass spectral glycoproteomic site mapping was used to identify alterations in the O-fucosylation of EGFs containing the selected mutation. One of the variants had few effects, two lead to a gain of function (GOF) and six to a loss of function (LOF). Most GOF and LOF could be associated with a change in O-fucosylation. Finally, by comparing our results with known NOTCH1 alterations in cancers from which our mutations originated, we were able to establish a correlation between our results and the known GOF or LOF of NOTCH1 in these cancers. This study shows that point mutations in NOTCH1 can lead to alterations in O-fucosylation that deregulate the Notch pathway and be associated with cancer processes.
2022-10-21 | PXD036345 | Pride
Project description:To understand how the NAC transcription factor KIL1 regulates age-induced senescence and cell death in maize silks, we need to get a genome-wide view on its downstream targets. We propose to compare the transcriptome profiles of GOF and LOF transgenic silk tissue with the profile of wild-type B104 silk. 1 cm of basal part of silk from rings 6-10 from plants harboring the dominant-negative repressor proSILK1:KIL1-SRDX, proSILK1:KIL1 overexpressing line, and wild type B104 will be harvested at 11 DASE. This will allow to compare and contrast the expression profiles of KIL1 LOF and GOF mutants with transcriptome data derived from wild type senescent silk.
2022-08-16 | E-MTAB-10850 | biostudies-arrayexpress
Project description:The aim of this study is to understand the mechanisms of TDP-43 neurotoxicity. Here, we perform a RNA-Seq analysis in TDP-43 gain-of-fucntion (GOF) , TDP-43 loss-of-function and wild-type late pupae heads (73-90 hours APF) and perform TDP-43 GOF vs wild type and TDP-43 LOF vs wild-type differential expression analysis to show that both mechanisms presents defects in ecdysone receptor (ECR)-dependeint transcriptional program switching, and strongly deregulate expression from the neuronal microtubule associated protien Map205.
2013-01-22 | GSE42844 | GEO
Project description:Morphogenesis of an epithelium relies on the differentiation of cellular territories that further adopt specific cell behavior. During dorsal closure of the Drosophila embryo, distinct territories and several signaling pathways (JNK, Wingless, Dpp, …) bring their own contribution to the migration of the epithelial sheets. In particular, the ectodermal leading edge, which is specified by the JNK pathway, behaves as a purse-string under the action of an acto-myosin cable and as a zipper under the action of cellular extensions. How the leading edge, which is supposed to be a uniform raw of cell, integrates the input of the different signaling pathways is poorly understood. We used microarrays to identify genes whose expression is regulated by the JNK pathway during dorsal closure of the Drosophila embryo. Three genetic conditions were compared: wild-type (WT), gain of function (GOF) and loss of function (LOF). For the GOF embryos, the JNK pathway was strongly activated by expressing HepACT in the ectoderm using the UAS-GAL4 system (69B-GAL4). For the LOF embryos, we used a combination of 2 alleles, heprev75 and hep1. Carefully staged embryos, corresponding to stages 13 and 14, were collected and for each condition, three independent RNA samples were prepared to be hybridized on the microarrays.
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Project description:Two-dimensional patterning of the follicular epithelium in Drosophila oogenesis is required for the formation of three-dimensional eggshell structures. Our analysis of a large number of published gene expression patterns in the follicle cells suggests that they follow a simple combinatorial code based on six spatial building blocks and the operations of union, difference, intersection, and addition. The building blocks are related to the distribution of inductive signals, provided by the highly conserved epidermal growth factor receptor and Decapentaplegic (DPP) pathways. We demonstrate the validity of the code by testing it against a set of patterns obtained in a large-scale transcriptional profiling experiment. Using the proposed code, we distinguish 36 distinct patterns for 81 genes expressed in the follicular epithelium and characterize their joint dynamics over four stages of oogenesis. The proposed combinatorial framework allows systematic analysis of the diversity and dynamics of two-dimensional transcriptional patterns and guides future studies of gene regulation. Keywords: EGFR, BMP, gain/loss-of-function RNA was isolated from hand dissected, stage 9-10 egg chambers. Five genetic backgrounds were profiled including: wild type, EGFR gain of function, EGFR loss of function, BMP gain of function, and BMP loss of function. Three biological replicates were hybridized for each pathway perturbation. The samples were split across two rounds of hybridization. Each round of hybridizations included three biological replicates for wild type: The first round included EGFR gof, EGFR lof, BMP gof, and wild type controls A1-A3 (GSM313514-16). For these 12 arrays the extraction, labeling, and hybridization steps were done in parallel. The second round included the BMP lof and wild type controls B1-B3 (GSM313517-19). For these 6 arrays, the extraction, labeling, and hybridization steps were done in parallel.
2008-11-11 | E-GEOD-12477 | biostudies-arrayexpress
Project description:TP53, encoding for the tumor suppressor p53, is the most frequently mutated gene in human cancer. The selective pressures shaping its mutational spectrum, dominated by missense mutations, have remained enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated. We generated isogenic human leukemia cell lines of the most common TP53 missense mutations using CRISPR/Cas9. Functional, DNA binding, and transcriptional analyses revealed loss-of-function (LOF) without GOF effects of missense mutations. Comprehensive mutational scanning of p53 single amino acid variants demonstrated that DNA-binding domain missense variants exert dominant-negative effects (DNE). In mice, DNE of p53 missense variants confer a selective advantage on hematopoietic cells upon DNA damage in vivo. Clinical outcomes in acute myeloid leukemia patients showed no evidence of GOF for TP53 missense mutations. These findings establish dominant-negativity as the primary unit of selection for TP53 missense mutations in myeloid malignancies.
2019-08-30 | GSE131592 | GEO
Project description:TP53, encoding for the tumor suppressor p53, is the most frequently mutated gene in human cancer. The selective pressures shaping its mutational spectrum, dominated by missense mutations, have remained enigmatic, and neomorphic gain-of-function (GOF) activities have been implicated. We generated isogenic human leukemia cell lines of the most common TP53 missense mutations using CRISPR/Cas9. Functional, DNA binding, and transcriptional analyses revealed loss-of-function (LOF) without GOF effects of missense mutations. Comprehensive mutational scanning of p53 single amino acid variants demonstrated that DNA-binding domain missense variants exert dominant-negative effects (DNE). In mice, DNE of p53 missense variants confer a selective advantage on hematopoietic cells upon DNA damage in vivo. Clinical outcomes in acute myeloid leukemia patients showed no evidence of GOF for TP53 missense mutations. These findings establish dominant-negativity as the primary unit of selection for TP53 missense mutations in myeloid malignancies.
2019-08-30 | GSE131484 | GEO