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Results for “regulatory module”

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At least 325 records · Page 18Linked to original sources

PubMed2002

The gibberellin pathway mediates KNOTTED1-type homeobox function in plants with different body plans.

BACKGROUND: The shoot apical meristem (SAM) is an indeterminate structure that gives rise to the aerial parts of higher plants. Leaves arise from the differentiation of cells at the flanks of the SAM. Current evidence suggests that the precise regulation of KNOTTED1-like homeobox (KNOX) transcription factors is central to the acquisition of leaf versus meristem identity in a wide spectrum of plant species. Factors required to repress KNOX gene expression in leaves have recently been identified. Additional factors such as the CHD3 chromatin remodeling factor PICKLE (PKL) act to restrict meristematic activity in Arabidopsis leaves without repressing KNOX gene expression. Less is known regarding downstream targets of KNOX function. Recent evidence, however, has suggested that growth regulators may mediate KNOX activity in a variety of plant species. RESULTS: Here we show that reduced activity of the gibberellin (GA) growth regulator pathway promotes meristematic activity, both in the natural context of KNOX function in the SAM and upon ectopic KNOX expression in Arabidopsis leaves. We show that constitutive signaling through the GA pathway is detrimental to meristem maintenance. Furthermore, we provide evidence that one of the functions of the KNOX protein SHOOTMERISTEMLESS (STM) is to exclude transcription of the GA-biosynthesis gene AtGA20ox1 from the SAM. We also demonstrate that AtGA20ox1 transcript is reduced in the pkl mutant in a KNOX-independent manner. Moreover, we show a similar interaction between KNOX proteins and GA-biosynthesis gene expression in the tomato leaf and implicate this interaction in regulation of the dissected leaf form. CONCLUSIONS: We suggest that repression of GA activity by KNOX transcription factors is a key component of meristem function. Transfer of the KNOX/GA regulatory module from the meristem to the leaf may have contributed to the generation of the diverse leaf morphologies observed in higher plants.

Arabidopsis↗

PubMed1999

Evidence for functional conservation of a mammalian homologue of the light-responsive plant protein COP1.

Identified in Arabidopsis as a repressor of light-regulated development, the COP1 (constitutively photomorphogenic 1) protein is characterized by a RING-finger motif and a WD40 repeat domain [1]. The subcellular localization of COP1 is light-dependent. COP1 acts within the nucleus to repress photomorphogenic development, but light inactivates COP1 and diminishes its nuclear abundance [2]. Here, we report the identification of a mammalian COP1 homologue that contains all the structural features present in Arabidopsis COP1 (AtCOP1). When expressed in plant cells, a fusion protein comprising mammalian COP1 and beta-glucuronidase (GUS) responded to light by changing its subcellular localization pattern in a manner similar to AtCOP1. Whereas the mammalian COP1 was unable to rescue the defects of Arabidopsis cop1 mutants, expression of the amino-terminal half of mammalian COP1 in Arabidopsis interfered with endogenous COP1 function, resulting in a hyperphotomorphogenic phenotype. Therefore, the regulatory modules in COP1 proteins that are responsible for the signal-dependent subcellular localization are functionally conserved between higher plants and mammals, suggesting that mammalian COP1 may share a common mode of action with its plant counterpart in regulating development and cellular signaling.

Animals↗

PubMed2026

Hyperlactate-Associated Lysine Lactylome Remodeling in Laryngeal Squamous Cell Carcinoma.

Laryngeal squamous cell carcinoma (LSCC) lacks reliable biomarkers, and the roles of lactate metabolism and lysine lactylation (Kla) remain largely unknown. We profiled the lysine lactylome of LSCC, paired it with adjacent normal tissues, and integrated the data with quantitative proteomic and transcriptomic analyses. LSCC exhibited a hyperlactate-associated phenotype characterized by dysregulated lactate-related genes (LRGs), altered protein abundance, increased tissue lactate, and globally increased Kla levels. Data-independent acquisition mass spectrometry (DIA-MS) identified 1616 Kla sites on 1468 peptides from 688 proteins, with most differential sites being upregulated in tumors. Differentially lactylated proteins were enriched in cell-matrix adhesion, cell migration, chromatin remodeling, and gene-regulatory processes and were clustered into cytoskeletal and nuclear regulatory modules. Multiple Kla sites were also detected on the core histones. Immunoblotting and tissue microarray analyses confirmed increased pan-Kla expression in the LSCC. Pan-Kla levels were independent of sex and age but positively correlated with the tumor stage and lymph-node metastasis. These findings provide a systematic resource for hyperlactate-associated lactylome remodeling in LSCCs and identify candidate Kla-related molecular features associated with clinicopathological progression for future functional and clinical evaluation.

Humans↗

PubMed2001

Analysis of barley chloroplast psbD light-responsive promoter elements in transplastomic tobacco.

The plastid gene psbD encodes D2, a photosystem II reaction center chlorophyll-binding protein. psbD is transcribed from a conserved chloroplast promoter that is activated by blue, white, or UV-A light. In this study, various forms of the barley (Hordeum vulgare L.) chloroplast psbD-LRP were fused to the uidA reporter gene and introduced into the tobacco (Nicotiana tabacum L.) plastid genome through homologous recombination. Primer extension analysis of transcripts from the psbD-LRP-uidA construct showed that the barley psbD-LRP was activated in tobacco by blue or white light. Transcription from this construct was also regulated by circadian cycling indicating that the barley psbD-LRP could respond to light modulated regulatory pathways in tobacco. Mutation of the psbD-LRP prokaryotic -10 promoter element reduced transcription to very low levels in all light regimes. In contrast, mutation of a prokaryotic -35 promoter element had no effect on transcription from the psbD-LRP. Deletion or mutation of an upstream activating element, the AAG-box (-36 to -64), also reduced transcription from the construct to very low levels. In contrast, deletion of the upstream PGT-box (-71 to -100) did not alter promoter activation by blue light, or responsiveness to circadian cycling. These in vivo studies confirm the importance of the psbD-LRP -10 promoter element and AAG-box in light regulation and demonstrate that these elements are sufficient to mediate circadian cycling of the barley psbD promoter.

Base Sequence↗

PubMed2002

Conscious processing of sexual information: interference caused by sexual primes.

The concept Sexual Content-Induced Delay (SCID) refers to a hesitancy in decision making related to erotic material (Geer & Bellard, 1996; Geer & Melton, 1997). Empirical evidence about SCID stems from lexical decision tasks. Our previous studies also showed SCID effects in sex versus neutral categorization tasks in which pictures were used. In these tasks, recognition of sexual pictures is delayed when preceded by consciously presented sexual primes. In the current study, 2 manipulations were added to the categorization task to investigate underlying information processing mechanisms of SCID. Firstly, the appraisal process was influenced by varying the instructions. Secondly, primes with nonsexual emotional content were added to test the specificity of the SCID effect. Thirty-seven undergraduates were asked to categorize sexual and neutral pictures that were primed by sexual, threatening, and neutral primes. Participants ignored or focussed prime content dependent on 2 different instructions. Results showed that the SCID effect only emerged when sexual primes were ignored; however, threatening primes also decelerated recognition of sexual pictures after the ignore instruction. Results of the focus instruction were qualitatively different, that is, participants recognized sexual pictures faster when primed sexually. It was suggested that SCID can be interpreted as the activation of regulatory modules by emotional stimuli in the stage of elicitation of emotional response. In contrast, when the sexual system is already activated, it appears that decisions regarding sexual information are facilitated.

Adult↗

PubMed1993

An electron microscopic immunogold analysis of developmental up-regulation of the blood-brain barrier GLUT1 glucose transporter.

Electron microscopy was used to quantitate blood-brain barrier (BBB) glucose transporters in newborn, 14-day-old suckling, 28-day-old weanling, and adult rabbits. A rabbit polyclonal antiserum to a synthetic peptide encoding the 13 C-terminal amino acids of the human erythrocyte glucose transporter (GLUT1) was labeled with 10-nm gold particle-secondary antibody conjugates and localized immunoreactive GLUT1 molecules in rabbit brain capillary endothelia. Three distinct populations of brain capillary profiles were identified in newborn rabbits: prepatent capillary buds, partially patent capillaries with highly amplified luminal membranes, and patent capillaries. Immunogold analyses indicated that the GLUT1 transporter abundance positively correlated with capillary developmental status. The mean number of gold particles per capillary profile increased at each developmental age examined, suggesting that developmental up-regulation of the BBB glucose transporter occurred in rabbits. GLUT1 immunoreactivity was three- to fourfold greater on the abluminal than luminal capillary membranes among all ages examined. Changes in the proportions of GLUT1 transporter were also seen, and possible reasons for the postnatal decrease in the percentage of cytoplasmic GLUT1 transporter are discussed. The numbers of cytoplasmic and membrane-associated immunogold particles increased with age. We conclude that regulatory modulations of BB glucose transport may be characterized by increases in BBB glucose transporter density with age and state of development. In addition, modulation of glucose transporter activity may be reflected by minor postnatal shifts of GLUT1 from cytoplasmic to membrane compartments, which can be demonstrated with quantitative immunogold electron microscopy.

Aging↗

PubMed2005

Global analysis of protein phosphorylation in yeast.

Protein phosphorylation is estimated to affect 30% of the proteome and is a major regulatory mechanism that controls many basic cellular processes. Until recently, our biochemical understanding of protein phosphorylation on a global scale has been extremely limited; only one half of the yeast kinases have known in vivo substrates and the phosphorylating kinase is known for less than 160 phosphoproteins. Here we describe, with the use of proteome chip technology, the in vitro substrates recognized by most yeast protein kinases: we identified over 4,000 phosphorylation events involving 1,325 different proteins. These substrates represent a broad spectrum of different biochemical functions and cellular roles. Distinct sets of substrates were recognized by each protein kinase, including closely related kinases of the protein kinase A family and four cyclin-dependent kinases that vary only in their cyclin subunits. Although many substrates reside in the same cellular compartment or belong to the same functional category as their phosphorylating kinase, many others do not, indicating possible new roles for several kinases. Furthermore, integration of the phosphorylation results with protein-protein interaction and transcription factor binding data revealed novel regulatory modules. Our phosphorylation results have been assembled into a first-generation phosphorylation map for yeast. Because many yeast proteins and pathways are conserved, these results will provide insights into the mechanisms and roles of protein phosphorylation in many eukaryotes.

Eukaryotic Cells↗

PubMed2006

The genetic basis for differences in leaf form between Arabidopsis thaliana and its wild relative Cardamine hirsuta.

A key question in biology is how differences in gene function or regulation produce new morphologies during evolution. Here we investigate the genetic basis for differences in leaf form between two closely related plant species, Arabidopsis thaliana and Cardamine hirsuta. We report that in C. hirsuta, class I KNOTTED1-like homeobox (KNOX) proteins are required in the leaf to delay cellular differentiation and produce a dissected leaf form, in contrast to A. thaliana, in which KNOX exclusion from leaves results in a simple leaf form. These differences in KNOX expression arise through changes in the activity of upstream gene regulatory sequences. The function of ASYMMETRIC LEAVES1/ROUGHSHEATH2/PHANTASTICA (ARP) proteins to repress KNOX expression is conserved between the two species, but in C. hirsuta the ARP-KNOX regulatory module controls new developmental processes in the leaf. Thus, evolutionary tinkering with KNOX regulation, constrained by ARP function, may have produced diverse leaf forms by modulating growth and differentiation patterns in developing leaf primordia.

Arabidopsis↗

PubMed2005

Are innate immune signaling pathways in plants and animals conserved?

Although adaptive immunity is unique to vertebrates, the innate immune response seems to have ancient origins. Common features of innate immunity in vertebrates, invertebrate animals and plants include defined receptors for microbe-associated molecules, conserved mitogen-associated protein kinase signaling cascades and the production of antimicrobial peptides. It is commonly reported that these similarities in innate immunity represent a process of divergent evolution from an ancient unicellular eukaryote that pre-dated the divergence of the plant and animal kingdoms. However, at present, data suggest that the seemingly analogous regulatory modules used in plant and animal innate immunity are a consequence of convergent evolution and reflect inherent constraints on how an innate immune system can be constructed.

Adaptor Proteins, Vesicular Transport↗

PubMed2003

Regulation of neuronal SNARE assembly by the membrane.

In the neuron, SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) assembly acts centrally in driving membrane fusion, a required process for neurotransmitter release. In the cytoplasm, vesicular SNARE VAMP-2 (vesicle-associated membrane protein-2) engages with two plasma membrane SNAREs, syntaxin 1A and SNAP-25 (synaptosome-associated protein of 25 kDa), to form the core complex that bridges two membranes. Although various factors regulate SNARE assembly, the membrane also aids in regulation by trapping VAMP-2 in the membrane. Fluorescence and EPR analyses revealed that the insertion of seven C-terminal core-forming residues into the membrane controls complex formation of the entire core region, even though the preceding 54 core-forming residues are fully exposed and freely moving. When two interfacial tryptophan residues in this region were replaced with hydrophilic serine residues, the mutation supported rapid complex formation. The results suggest that the membrane-proximal region of VAMP-2 is a regulatory module for SNARE assembly, providing new insights into calcium-triggered membrane fusion.

Antigens, Surface↗

PubMed2026

Natural variation in BRN1 enhances nitrogen sensitivity to improve rice nitrogen use efficiency.

Green Revolution rice varieties deliver high yields but require excessive nitrogen (N) fertilizer and show diminished N responsiveness, severely reducing nitrogen-use efficiency (NUE). To dissect the molecular basis of low N sensitivity in modern cultivars, we conducted a genome-wide association study (GWAS) for biomass response to N (BRN), a trait tightly linked to N sensitivity, using a diverse rice germplasm panel. We identified BRN1 as a key regulator of N-dependent biomass accumulation that regulates NLP3, a master transcription factor governing nitrate signaling. Under elevated N supply, the strigolactone signaling repressor D53 accumulates substantially and interacts with BRN1 to repress NLP3 transcription, thereby reducing rice N response. Notably, the high-response BRN1H allele encodes a more stable protein that alleviates D53-mediated suppression. Introgression of this allele into modern cultivars significantly enhanced N sensitivity and grain yield under both low and high N conditions. Our findings establish a D53-BRN1-NLP3 regulatory module controlling rice NUE, providing a target for rice breeding to sustain high productivity with improved resource sustainability.

Oryza↗

PubMed2006

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes.

OBJECTIVE: Human adenovirus Ad-36 causes adiposity in animal models and shows association with human obesity. Ad-36 enhances differentiation of 3T3-L1 and human preadipocytes, without cell lysis, a characteristic that may contribute to its adipogenic effect observed in vivo. Ad-2, another human adenovirus is nonadipogenic in animals and in 3T3-L1 cells and shows no correlation with human obesity. The objective of this study was to determine the adipogenic roles of viral mRNA and DNA, which may explain the differential effects of Ad-36 and Ad-2 on preadipocyte differentiation. METHODS: This study determined the duration of selected Ad-36 gene expression in 3T3-L1 cells, and the effect on preadipocytes differentiation, when Ad-36 gene expression was attenuated by Cidofovir, an antiadenoviral agent. RESULTS: The results showed that Ad-36, but not Ad-2, expresses viral mRNA. Ad-36 gene expression peaked at 2-4 days postinoculation and very low levels persisted after day 7. Despite the viral mRNA expression, Ad-36 infection of 3T3-L1 cells was abortive as indicated by a progressive decrease in viral DNA quantity. Attenuation of Ad-36 mRNA expression by Cidofovir reduced the adipogenic effect of the virus. CONCLUSION: In conclusion, viral mRNA expression, although transient, is a prerequisite for enhancing differentiation of preadipocytes by Ad-36. Viral DNA replication was not required for the effect. This is the first evidence for the role of gene expression of an adipogenic human virus in enhancing preadipocytes differentiation. This study provides the basis for further understanding novel regulatory modulators of preadipocytes differentiation.

3T3-L1 Cells↗

PubMed1981

UDP-galactose:ceramide galactosyltransferase of rat central-nervous-system myelin.

The properties of ceramide galactosyltransferase associated with myelin and microsomal fractions of rat brain were studied. The enzyme from both the fractions had similar properties during development and synthesized the same molecular species of the product cerebroside. The results suggested that during myelination the turnover rate of enzyme protein is altered instead of regulatory modulation of the enzyme protein.

Animals↗

PubMed1996

Domain-structure analysis of recombinant rat hormone-sensitive lipase.

Hormone-sensitive lipase (HSL) plays a key role in lipid metabolism and overall energy homoeostasis, by controlling the release of fatty acids from stored triglycerides in adipose tissue. Lipases and esterases form a protein superfamily with a common structural fold, called the alpha/beta-hydrolase fold, and a catalytic triad of serine, aspartic or glutamic acid and histidine. Previous alignments between HSL and lipase 2 of Moraxella TA144 have been extended to cover a much larger part of the HSL sequence. From these extended alignments, possible sites for the catalytic triad and alpha/beta-hydrolase fold are suggested. Furthermore, it is proposed that HSL contains a structural domain with catalytic capacity and a regulatory module attached, as well as a structural N-terminal domain unique to this enzyme. In order to test the proposed domain structure, rat HSL was overexpressed and purified to homogeneity using a baculovirus/insect-cell expression system. The purification, resulting in > 99% purity, involved detergent solubilization followed by anion-exchange chromatography and hydrophobic-interaction chromatography. The purified recombinant enzyme was identical to rat adipose-tissue HSL with regard to specific activity, substrate specificity and ability to serve as a substrate for cAMP-dependent protein kinase. The recombinant HSL was subjected to denaturation by guanidine hydrochloride and limited proteolysis. These treatments resulted in more extensive loss of activity against phospholipid-stabilized lipid substrates than against water-soluble substrates, suggesting that the hydrolytic activity can be separated from recognition of lipid substrates. These data support the concept that HSL has at least two major domains.

Amino Acid Sequence↗

PubMed2004

Structural basis of activity and allosteric control of diguanylate cyclase.

Recent discoveries suggest that a novel second messenger, bis-(3'-->5')-cyclic di-GMP (c-diGMP), is extensively used by bacteria to control multicellular behavior. Condensation of two GTP to the dinucleotide is catalyzed by the widely distributed diguanylate cyclase (DGC or GGDEF) domain that occurs in various combinations with sensory and/or regulatory modules. The crystal structure of the unorthodox response regulator PleD from Caulobacter crescentus, which consists of two CheY-like receiver domains and a DGC domain, has been solved in complex with the product c-diGMP. PleD forms a dimer with the CheY-like domains (the stem) mediating weak monomer-monomer interactions. The fold of the DGC domain is similar to adenylate cyclase, but the nucleotide-binding mode is substantially different. The guanine base is H-bonded to Asn-335 and Asp-344, whereas the ribosyl and alpha-phosphate moieties extend over the beta2-beta3-hairpin that carries the GGEEF signature motif. In the crystal, c-diGMP molecules are crosslinking active sites of adjacent dimers. It is inferred that, in solution, the two DGC domains of a dimer align in a two-fold symmetric way to catalyze c-diGMP synthesis. Two mutually intercalated c-diGMP molecules are found tightly bound at the stem-DGC interface. This allosteric site explains the observed noncompetitive product inhibition. We propose that product inhibition is due to domain immobilization and sets an upper limit for the concentration of this second messenger in the cell.

Allosteric Regulation↗

PubMed2005

The role of binding site cluster strength in Bicoid-dependent patterning in Drosophila.

The maternal morphogen Bicoid (Bcd) is distributed in an embryonic gradient that is critical for patterning the anterior-posterior (AP) body plan in Drosophila. Previous work identified several target genes that respond directly to Bcd-dependent activation. Positioning of these targets along the AP axis is thought to be controlled by cis-regulatory modules (CRMs) that contain clusters of Bcd-binding sites of different "strengths." Here we use a combination of Bcd-site cluster analysis and evolutionary conservation to predict Bcd-dependent CRMs. We tested 14 predicted CRMs by in vivo reporter gene assays; 11 show Bcd-dependent activation, which brings the total number of known Bcd target elements to 21. Some CRMs drive expression patterns that are restricted to the most anterior part of the embryo, whereas others extend into middle and posterior regions. However, we do not detect a strong correlation between AP position of target gene expression and the strength of Bcd site clusters alone. Rather, we find that binding sites for other activators, including Hunchback and Caudal correlate with CRM expression in middle and posterior body regions. Also, many Bcd-dependent CRMs contain clusters of sites for the gap protein Kruppel, which may limit the posterior extent of activation by the Bcd gradient. We propose that the key design principle in AP patterning is the differential integration of positive and negative transcriptional information at the level of individual CRMs for each target gene.

Animals↗

PubMed2006

Global mapping of c-Myc binding sites and target gene networks in human B cells.

The protooncogene MYC encodes the c-Myc transcription factor that regulates cell growth, cell proliferation, cell cycle, and apoptosis. Although deregulation of MYC contributes to tumorigenesis, it is still unclear what direct Myc-induced transcriptomes promote cell transformation. Here we provide a snapshot of genome-wide, unbiased characterization of direct Myc binding targets in a model of human B lymphoid tumor using ChIP coupled with pair-end ditag sequencing analysis (ChIP-PET). Myc potentially occupies > 4,000 genomic loci with the majority near proximal promoter regions associated frequently with CpG islands. Using gene expression profiles with ChIP-PET, we identified 668 direct Myc-regulated gene targets, including 48 transcription factors, indicating that Myc is a central transcriptional hub in growth and proliferation control. This first global genomic view of Myc binding sites yields insights of transcriptional circuitries and cis regulatory modules involving Myc and provides a substantial framework for our understanding of mechanisms of Myc-induced tumorigenesis.

B-Lymphocytes↗

PubMed2002

Genes directly controlled by CtrA, a master regulator of the Caulobacter cell cycle.

Studies of the genetic network that controls the Caulobacter cell cycle have identified a response regulator, CtrA, that controls, directly or indirectly, one-quarter of the 553 cell cycle-regulated genes. We have performed in vivo genomic binding site analysis of the CtrA protein to identify which of these genes have regulatory regions bound directly by CtrA. By combining these data with previous global analysis of cell cycle transcription patterns and gene expression profiles of mutant ctrA strains, we have determined that CtrA directly regulates at least 95 genes. The total group of CtrA-regulated genes includes those involved in polar morphogenesis, DNA replication initiation, DNA methylation, cell division, and cell wall metabolism. Also among the genes in this notably large regulon are 14 that encode regulatory proteins, including 10 two-component signal transduction regulatory proteins. Identification of additional regulatory genes activated by CtrA will serve to directly connect new regulatory modules to the network controlling cell cycle progression.

Amino Acid Motifs↗