scholarly journals MEK1 and Protein Phosphatase 4 Coordinate Dictyostelium Development and Chemotaxis

2007 ◽  
Vol 27 (10) ◽  
pp. 3817-3827 ◽  
Author(s):  
Michelle C. Mendoza ◽  
Ezgi O. Booth ◽  
Gad Shaulsky ◽  
Richard A. Firtel

ABSTRACT The MEK and extracellular signal-regulated kinase/mitogen-activated protein kinase proteins are established regulators of multicellular development and cell movement. By combining traditional genetic and biochemical assays with a statistical analysis of global gene expression profiles, we discerned a genetic interaction between Dictyostelium discoideum mek1, smkA (named for its role in the suppression of the mek1 − mutation), and pppC (the protein phosphatase 4 catalytic subunit gene). We found that during development and chemotaxis, both mek1 and smkA regulate pppC function. In other organisms, the protein phosphatase 4 catalytic subunit, PP4C, functions in a complex with the regulatory subunits PP4R2 and PP4R3 to control recovery from DNA damage. Here, we show that catalytically active PP4C is also required for development, chemotaxis, and the expression of numerous genes. The product of smkA (SMEK) functions as the Dictyostelium PP4R3 homolog and positively regulates a subset of PP4C's functions: PP4C-mediated developmental progression, chemotaxis, and the expression of genes specifically involved in cell stress responses and cell movement. We also demonstrate that SMEK does not control the absolute level of PP4C activity and suggest that SMEK regulates PP4C by controlling its localization to the nucleus. These data define a novel genetic pathway in which mek1 functions upstream of pppC-smkA to control multicellular development and chemotaxis.

2020 ◽  
Vol 318 (3) ◽  
pp. G419-G427 ◽  
Author(s):  
Tatsuhide Nabeshima ◽  
Shin Hamada ◽  
Keiko Taguchi ◽  
Yu Tanaka ◽  
Ryotaro Matsumoto ◽  
...  

The activation of the Kelch-like ECH-associated protein 1 (Keap1)-NF-E2-related factor 2 (Nrf2) pathway contributes to cancer progression in addition to oxidative stress responses. Loss-of-function Keap1 mutations were reported to activate Nrf2, leading to cancer progression. We examined the effects of Keap1 deletion in a cholangiocarcinoma mouse model using a mutant K-ras/ p53 mouse. Introduction of the Keap1 deletion into liver-specific mutant K-ras/ p53 expression resulted in the formation of invasive cholangiocarcinoma. Comprehensive analyses of the gene expression profiles identified broad upregulation of Nrf2-target genes such as Nqo1 and Gstm1 in the Keap1-deleted mutant K-ras/ p53 expressing livers, accompanied by upregulation of cholangiocyte-related genes. Among these genes, the transcriptional factor Sox9 was highly expressed in the dysplastic bile duct. The Keap-Nrf2-Sox9 axis might serve as a novel therapeutic target for cholangiocarcinoma. NEW & NOTEWORTHY The Keap1-Nrf2 system has a wide variety of effects in addition to the oxidative stress response in cancer cells. Addition of the liver-specific Keap1 deletion to mice harboring mutant K-ras and p53 accelerated cholangiocarcinoma formation, together with the hallmarks of Nrf2 activation. This process involved the expansion of Sox9-positive cells, indicating increased differentiation toward the cholangiocyte phenotype.


Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 927
Author(s):  
Xifang Zong ◽  
Qi Yan ◽  
Fan Wu ◽  
Qian Ma ◽  
Jiyu Zhang

Plant-specific NAC (NAM, ATAF, CUC) transcription factor (TF) family plays important roles in biological processes such as plant growth and response to stress. Nevertheless, no information is known about NAC TFs in Cleistogenes songorica, a prominent xerophyte desert grass in northwestern China. In this study, 162 NAC genes were found from the Cleistogenes songorica genome, among which 156 C. songoricaNAC (CsNAC) genes (96.3%) were mapped onto 20 chromosomes. The phylogenetic tree constructed by CsNAC and rice NAC TFs can be separated into 14 subfamilies. Syntenic and Ka/Ks analyses showed that CsNACs were primarily expanded by genomewide replication events, and purifying selection was the primary force driving the evolution of CsNAC family genes. The CsNAC gene expression profiles showed that 36 CsNAC genes showed differential expression between cleistogamous (CL) and chasmogamous (CH) flowers. One hundred and two CsNAC genes showed differential expression under heat, cold, drought, salt and ABA treatment. Twenty-three CsNAC genes were commonly differentially expressed both under stress responses and during dimorphic floret development. Gene Ontology (GO) annotation, coexpression network and qRT-PCR tests revealed that these CsNAC genes may simultaneously regulate dimorphic floret development and the response to stress. Our results may help to characterize the NAC transcription factors in C. songorica and provide new insights into the functional research and application of the NAC family in crop improvement, especially in dimorphic floret plants.


2020 ◽  
Vol 21 (5) ◽  
pp. 1879 ◽  
Author(s):  
Shanshan He ◽  
Gaopeng Yuan ◽  
Shuxun Bian ◽  
Xiaolei Han ◽  
Kai Liu ◽  
...  

Major latex proteins (MLPs) play critical roles in plants defense and stress responses. However, the roles of MLPs from apple (Malus × domestica) have not been clearly identified. In this study, we focused on the biological role of MdMLP423, which had been previously characterized as a potential pathogenesis-related gene. Phylogenetic analysis and conserved domain analysis indicated that MdMLP423 is a protein with a ‘Gly-rich loop’ (GXGGXG) domain belonging to the Bet v_1 subfamily. Gene expression profiles showed that MdMLP423 is mainly expressed in flowers. In addition, the expression of MdMLP423 was significantly inhibited by Botryosphaeria berengeriana f. sp. piricola (BB) and Alternaria alternata apple pathotype (AAAP) infections. Apple calli overexpressing MdMLP423 had lower expression of resistance-related genes, and were more sensitive to infection with BB and AAAP compared with non-transgenic calli. RNA-seq analysis of MdMLP423-overexpressing calli and non-transgenic calli indicated that MdMLP423 regulated the expression of a number of differentially expressed genes (DEGs) and transcription factors, including genes involved in phytohormone signaling pathways, cell wall reinforcement, and genes encoding the defense-related proteins, AP2-EREBP, WRKY, MYB, NAC, Zinc finger protein, and ABI3. Taken together, our results demonstrate that MdMLP423 negatively regulates apple resistance to BB and AAAP infections by inhibiting the expression of defense- and stress-related genes and transcription factors.


2001 ◽  
Vol 5 (4) ◽  
pp. 161-170 ◽  
Author(s):  
DAVID GERHOLD ◽  
MEIQING LU ◽  
JIAN XU ◽  
CHRISTOPHER AUSTIN ◽  
C. THOMAS CASKEY ◽  
...  

Oligonucleotide DNA microarrays were investigated for utility in measuring global expression profiles of drug metabolism genes. This study was performed to investigate the feasibility of using microarray technology to minimize the long, expensive process of testing drug candidates for safety in animals. In an evaluation of hybridization specificity, microarray technology from Affymetrix distinguished genes up to a threshold of ∼90% DNA identity. Oligonucleotides representing human cytochrome P-450 gene CYP3A5 showed heterologous hybridization to CYP3A4 and CYP3A7 RNAs. These genes could be clearly distinguished by selecting a subset of oligonucleotides that hybridized selectively to CYP3A5. Further validation of the technology was performed by measuring gene expression profiles in livers of rats treated with vehicle, 3-methylcholanthrene (3MC), phenobarbital, dexamethasone, or clofibrate and by confirming data for six genes using quantitative RT-PCR. Responses of drug metabolism genes, including CYPs, epoxide hydrolases ( EHs), UDP-glucuronosyl transferases ( UGTs), glutathione sulfotransferases ( GSTs), sulfotransferases ( STs), drug transporter genes, and peroxisomal genes, to these well-studied compounds agreed well with, and extended, published observations. Additional gene regulatory responses were noted that characterize metabolic effects or stress responses to these compounds. Thus microarray technology can provide a facile overview of gene expression responses relevant to drug metabolism and toxicology.


2017 ◽  
Author(s):  
Maya Khasin ◽  
Rebecca E. Cahoon ◽  
Sophie Alvarez ◽  
Richard Beckeris ◽  
Seong-il Eyun ◽  
...  

AbstractAbscisic acid (ABA) is a phytohormone that has been extensively characterized in higher plants for its roles in seed and bud dormancy, leaf abscission, and stress responses. Genomic studies have identified orthologs for ABA-related genes throughout the Viridiplantae, including in unicellular algae; however, the role of ABA in algal physiology has not been characterized, and the existence of such a role has been a matter of dispute. In this study, we demonstrate that ABA is involved in regulating algal stress responses. Chlorella sorokiniana strain UTEX 1230 contains genes orthologous to those of higher plants which are essential for ABA biosynthesis, sensing, and degradation. RNAseq-based transcriptomic studies reveal that treatment with ABA induces dramatic changes in gene expression profiles, including the induction of a subset of genes involved in DNA replication and repair, a phenomenon which has been demonstrated in higher plants. Pretreatment of C. sorokiniana cultures with ABA exerts a protective effect on cell viability in response to ultraviolet radiation. Additionally, C. sorokiniana produces and secretes biologically relevant amounts of both ABA and the oxylipin 12-oxo-phytodienoic acid (OPDA) into the growth medium in response to abiotic stressors. Taken together, these phenomena suggest that ABA signaling evolved as an intercellular stress response signaling molecule in eukaryotic microalgae prior to the evolution of multicellularity and colonization of land.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Khadeeja Siddique ◽  
Eirill Ager-Wick ◽  
Romain Fontaine ◽  
Finn-Arne Weltzien ◽  
Christiaan V. Henkel

AbstractThe pituitary is the vertebrate endocrine gland responsible for the production and secretion of several essential peptide hormones. These, in turn, control many aspects of an animal’s physiology and development, including growth, reproduction, homeostasis, metabolism, and stress responses. In teleost fish, each hormone is presumably produced by a specific cell type. However, key details on the regulation of, and communication between these cell types remain to be resolved. We have therefore used single-cell sequencing to generate gene expression profiles for 2592 and 3804 individual cells from the pituitaries of female and male adult medaka (Oryzias latipes), respectively. Based on expression profile clustering, we define 15 and 16 distinct cell types in the female and male pituitary, respectively, of which ten are involved in the production of a single peptide hormone. Collectively, our data provide a high-quality reference for studies on pituitary biology and the regulation of hormone production, both in fish and in vertebrates in general.


2018 ◽  
Vol 140 (2) ◽  
pp. 87-96
Author(s):  
Haitao Xu ◽  
Fusheng Yao

Waldenström macroglobulinemia (WM), also known as lymphoplasmacytic lymphoma, is rare but a clinicopathologically distinct B-cell malignancy. This study assessed differentially expressed genes (DEGs) to identify potential WM biomarkers and uncover the underlying the molecular mechanisms of WM progression using gene expression profiles from the Gene Expression Omnibus database. DEGs were identified using the LIMMA package and their potential functions were then analyzed by using the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and the protein-protein interaction (PPI) network analysis by using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Data showed that among 1,756 DEGs, 926 were upregulated and 830 were downregulated by comparing WM BM CD19+ with normal PB CD19+ B cell samples, whereas 241 DEGs (95 upregulated and 146 downregulated) were identified by comparing WM BM CD138+ with normal BM CD138+ plasma cell samples. The DEGs were enriched in different GO terms and pathways, including the apoptotic process, cell cycle arrest, immune response, cell adhesion, mitogen-activated protein kinase signaling pathway, toll-like receptor signaling pathway, and the gonadotropin-releasing hormone signaling pathway. Hub nodes in the PPI network included CDK1, JUN, CREBBP, EP300, CAD, CDK2, and MAPK14. Bioinformatics analysis of the GSE9656 dataset identified 7 hub genes that might play an important role in WM development and progression. Some of the candidate genes and pathways may serve as promising therapeutic targets for WM.


2016 ◽  
Vol 141 (5) ◽  
pp. 490-497 ◽  
Author(s):  
Xiaojuan Zong ◽  
Jiawei Wang ◽  
Li Xu ◽  
Hairong Wei ◽  
Xin Chen ◽  
...  

Improving the poor resistance to environmental stress and the weak development of roots system in the cherry (Prunus) rootstock ‘Gisela 6’ (Prunus cerasus × Prunus canescens) is of great importance for sustainable sweet cherry (Prunus avium) production. Although a stable genetic transformation system has been developed for ‘Gisela 6’ rootstock, there is little information on the identification of genes involved in stress resistance. Using the cherry rootstock cultivar Gisela 6, we identified a total of 12 novel mitogen-activated protein kinase (MAPK) genes, designated PcMPKs. Phylogenetic analysis revealed that the PcMPKs could be divided into four groups, designated A, B, C, and D. In addition, an intron–exon structure analysis for the PcMPKs was conducted to help further understand the structure–function relationships within the cherry family. The expression profiles of PcMPKs in response to abiotic and biotic stresses were characterized using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Five PcMPKs (i.e., PcMPK4-1, PcMPK4-2, PcMPK3, PcMPK6, and PcMPK18) exhibited differential expression, and suggested their potential roles in plant responding to various stresses. This study provides the basis for further analysis on the physiological functions of PcMPKs in environmental tolerance in cherry rootstocks.


2008 ◽  
Vol 19 (4) ◽  
pp. 1519-1528 ◽  
Author(s):  
Haixia Wang ◽  
Qing Xu ◽  
Fang Xiao ◽  
Yong Jiang ◽  
Zhenguo Wu

We and others previously showed that p38 mitogen-activated protein kinase is indispensable for myogenic differentiation. However, it is less clear which of the four p38 isoforms in the mouse genome participates in this process. Using C2C12 myogenic cells as a model, we showed here that p38α, β, and γ are expressed with distinct expression patterns during differentiation. Knockdown of any of them by small interfering RNA inhibits myogenic differentiation, which suggests that the functions of the three p38 isoforms are not completely redundant. To further elucidate the unique role of each p38 isoform in myogenic differentiation, we individually knocked down one p38 isoform at a time in C2C12 cells, and we compared the whole-genome gene expression profiles by microarrays. We found that some genes are coregulated by all three p38 isoforms, whereas others are uniquely regulated by one particular p38 isoform. Furthermore, several novel p38 target genes (i.e., E2F2, cyclin D3, and WISP1) are found to be required for myogenin expression, which provides a molecular basis to explain why different p38 isoforms are required for myogenic differentiation.


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