scholarly journals FOXO-regulated transcription restricts overgrowth of Tsc mutant organs

2008 ◽  
Vol 180 (4) ◽  
pp. 691-696 ◽  
Author(s):  
Kieran F. Harvey ◽  
Jaakko Mattila ◽  
Avi Sofer ◽  
F. Christian Bennett ◽  
Matthew R. Ramsey ◽  
...  

FOXO is thought to function as a repressor of growth that is, in turn, inhibited by insulin signaling. However, inactivating mutations in Drosophila melanogaster FOXO result in viable flies of normal size, which raises a question over the involvement of FOXO in growth regulation. Previously, a growth-suppressive role for FOXO under conditions of increased target of rapamycin (TOR) pathway activity was described. Here, we further characterize this phenomenon. We show that tuberous sclerosis complex 1 mutations cause increased FOXO levels, resulting in elevated expression of FOXO-regulated genes, some of which are known to antagonize growth-promoting pathways. Analogous transcriptional changes are observed in mammalian cells, which implies that FOXO attenuates TOR-driven growth in diverse species.

BMC Genetics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yue Hu ◽  
Yihe Zhang ◽  
Cong Liu ◽  
Rui Qin ◽  
Desheng Gong ◽  
...  

Abstract Background In order to study the relations of hepatocellular functions, weight gain and metabolic imbalance caused by low-dose antibiotics (LDA) via epigenetic regulation of gene transcription, 32 weaned piglets were employed as animal models and randomly allocated into two groups with diets supplemented with 0 or LDA (chlorotetracycline and virginiamycin). Results During the 4 weeks of the experiment, LDA showed a clear growth-promoting effect, which was exemplified by the significantly elevated body weight and average daily gain. Promoter methylome profiling using liquid hybridization capture-based bisulfite sequencing (LHC-BS) indicated that most of the 745 differential methylation regions (DMRs) were hypermethylated in the LDA group. Several DMRs were significantly enriched in genes related with fatty acids metabolic pathways, such as FABP1 and PCK1. In addition, 71 differentially expressed genes (DEGs) were obtained by strand-specific transcriptome analysis of liver tissues, including ALOX15, CXCL10 and NNMT, which are three key DEGs that function in lipid metabolism and immunity and which had highly elevated expression in the LDA group. In accordance with these molecular changes, the lipidome analyses of serum by LC-MS identified 38 significantly differential lipids, most of which were downregulated in the LDA group. Conclusions Our results indicate that LDA could induce epigenetic and transcriptional changes of key genes and lead to enhanced efficiency of lipid metabolism in the liver.


2017 ◽  
Author(s):  
Kurt Buhler ◽  
Jason Clements ◽  
Mattias Winant ◽  
Veerle Vulsteke ◽  
Patrick Callaerts

AbstractGrowth and maturation are coordinated processes in all animals. Integration of internal cues, such as signalling pathways, with external cues such as nutritional status is paramount for an orderly progression of development in function of growth. In Drosophila, this coordination involves insulin and steroid signalling, but the mechanisms by which this occurs and how they are coordinated are incompletely understood. We show that production of the bioactive 20-hydroxyecdysone by the enzyme Shade in the fat body is a nutrient-dependent process. We demonstrate that during fed conditions, Shade plays a role in growth regulation, as knockdown of shade in the fat body resulted in growth defects and perturbed expression and release of the Drosophila insulin-like peptides from the insulin-producing cells (IPCs). We identify the trachea and IPCs as direct targets through which 20-hydroxyecdysone regulates insulin-signaling. The identification of the trachea-dependent regulation of insulin-signaling exposes an important variable that may have been overlooked in other studies focusing on insulin-signaling in Drosophila. Finally, we show with IPC-specific manipulations that 20E may both be a growth-promoting and growth-inhibiting signal in the IPCs acting through different nuclear receptors. Our findings provide a potentially conserved, novel mechanism by which nutrition can modulate steroid hormone bioactivation, reveal an important caveat of a commonly used transgenic tool to study IPC function and yield further insights as to how steroid and insulin signalling are coordinated during development to regulate growth and developmental timing.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1665
Author(s):  
Natalia Nikonorova ◽  
Evan Murphy ◽  
Cassio Flavio Fonseca de Lima ◽  
Shanshuo Zhu ◽  
Brigitte van de Cotte ◽  
...  

Auxin plays a dual role in growth regulation and, depending on the tissue and concentration of the hormone, it can either promote or inhibit division and expansion processes in plants. Recent studies have revealed that, beyond transcriptional reprogramming, alternative auxin-controlled mechanisms regulate root growth. Here, we explored the impact of different concentrations of the synthetic auxin NAA that establish growth-promoting and -repressing conditions on the root tip proteome and phosphoproteome, generating a unique resource. From the phosphoproteome data, we pinpointed (novel) growth regulators, such as the RALF34-THE1 module. Our results, together with previously published studies, suggest that auxin, H+-ATPases, cell wall modifications and cell wall sensing receptor-like kinases are tightly embedded in a pathway regulating cell elongation. Furthermore, our study assigned a novel role to MKK2 as a regulator of primary root growth and a (potential) regulator of auxin biosynthesis and signalling, and suggests the importance of the MKK2 Thr31 phosphorylation site for growth regulation in the Arabidopsis root tip.


2013 ◽  
Vol 45 (8) ◽  
pp. 321-331 ◽  
Author(s):  
Gretchen A. Meyer ◽  
Simon Schenk ◽  
Richard L. Lieber

In this work, the interaction between the loss of a primary component of the skeletal muscle cytoskeleton, desmin, and two common physiological stressors, acute mechanical injury and aging, were investigated at the transcriptional, protein, and whole muscle levels. The transcriptional response of desmin knockout ( des −/−) plantarflexors to a bout of 50 eccentric contractions (ECCs) showed substantial overlap with the response in wild-type ( wt) muscle. However, changes in the expression of genes involved in muscle response to injury were blunted in adult des −/− muscle compared with wt (fold change with ECC in des −/− and wt, respectively: Mybph, 1.4 and 2.9; Xirp1, 2.2 and 5.7; Csrp3, 1.8 and 4.3), similar to the observed blunted mechanical response (torque drop: des −/− 30.3% and wt 55.5%). Interestingly, in the absence of stressors, des −/− muscle exhibited elevated expression of many these genes compared with wt. The largest transcriptional changes were observed in the interaction between aging and the absence of desmin, including many genes related to slow fiber pathway (Myh7, Myl3, Atp2a2, and Casq2) and insulin sensitivity (Tlr4, Trib3, Pdk3, and Pdk4). Consistent with these transcriptional changes, adult des −/− muscle exhibited a significant fiber type shift from fast to slow isoforms of myosin heavy chain ( wt, 5.3% IIa and 71.7% IIb; des −/−, 8.4% IIa and 61.4% IIb) and a decreased insulin-stimulated glucose uptake ( wt, 0.188 μmol/g muscle/20 min; des −/−, 0.085 μmol/g muscle/20 min). This work points to novel areas of influence of this cytoskeletal protein and directs future work to elucidate its function.


1980 ◽  
Vol 93 (2) ◽  
pp. 134-138 ◽  
Author(s):  
M. Donnadieu ◽  
R. M. Schimpff ◽  
P. Garnier ◽  
J. L. Chaussain ◽  
J. C. Job

Abstract. Since transferrin (Tf) in vitro has a growth-promoting activity and is associated with NSILA properties, the aim of this work was to study in vivo the relationships between Tf, somatomedin activity (SM), growth hormone (GH) secretion, and height velocity in children. An iv infusion of ornithine hydrochloride was given to 23 controls; the induced rise of GH was accompanied by a simultaneous fall of SM (r = −0.711, P < 0.001) and was preceded by a fall of Tf (r = −0.610, P < 0.01). In 17 obese children SM was within the normal range, when Tf levels were higher and arginineinduced GH peaks lower than in the controls, and a negative correlation was found between Tf basal levels and GH peaks (r = −0.608, P < 0.01). In 9 children with confirmed hypopituitarism the Tf levels were significantly lower than in the controls. In 14 children with confirmed or suspected hypopituitarism a single im injection of hGH (6 mg) failed to induce Tf variations over 24 h. In 39 of these children the height velocity was significantly correlated with Tf basal levels (r = 0.701, P < 0.001). These data suggest that transferrin is involved in growth regulation, and that GH secretion is related to transferrin levels by a feed-back mechanism.


1989 ◽  
Vol 2 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Yasushi Shintani ◽  
Keiji Iwamoto ◽  
Kazuaki Kitano

2005 ◽  
Vol 288 (6) ◽  
pp. R1423-R1431 ◽  
Author(s):  
Michael B. Reid

The ubiquitin-proteasome pathway plays a critical role in the adaptation of skeletal muscle to persistent decreases or increases in muscle activity. This article outlines the basics of pathway function and reviews what we know about pathway responses to altered muscle use. The ubiquitin-proteasome pathway regulates proteolysis in mammalian cells by attaching ubiquitin polymers to damaged proteins; this targets the protein for degradation via the 26S proteasome. The pathway is constitutively active in muscle and continually regulates protein turnover. Conditions of decreased muscle use, e.g., unloading, denervation, or immobilization, stimulate general pathway activity. This activity increase is caused by upregulation of regulatory components in the pathway and leads to accelerated proteolysis, resulting in net loss of muscle protein. Pathway activity is also increased in response to exercise, a two-phase response. An immediate increase in selective ubiquitin conjugation by constitutive pathway components contributes to exercise-stimulated signal transduction. Over hours-to-days, exercise also stimulates a delayed increase in general ubiquitin conjugating activity by inducing expression of key components in the pathway. This increase mediates a late-phase rise in protein degradation that is required for muscle adaptation to exercise. Thus the ubiquitin-proteasome pathway functions as an essential mediator of muscle remodeling, both in atrophic states and exercise training.


2019 ◽  
Vol 49 ◽  
pp. e1261 ◽  
Author(s):  
Yazmín C. Díaz-Martínez ◽  
Griselda K. Guillén ◽  
José E. Sánchez

Background: Certain microorganisms during the preparation of substrate for growing Agaricus bisporus are of great interest for the conversion of organic material and for the excretion of a wide range of metabolites with growth regulation activities that may affect the mycelial growth processes and mushroom yield. Adding beneficial microorganisms in the substrate may be a biotechnological alternative to optimize A. bisporus cultivation. Objective: Isolate and evaluate thermophilic microorganisms from self-heating pasteurized substrate with growth-promoting effects on A. bisporus cultivation. Methods: Different microorganisms were isolated and selected at 45 and 55 °C. They were tested for siderophore production, 1-octen-3-ol consumption, and phosphate solubilization in coculture with A. bisporus to determine their growth effects on potato dextrose agar (PDA) and on sterile pangola grass (Digitaria eriantha). Results: Of the 106 microorganisms isolated, 88 % were able to grow in the presence of 1-octen-3-ol, while 1 % had the capacity to produce siderophores, and 55 % had the ability to solubilize phosphate. The strains Bacillus hisashii ECS-B-65, B. licheniformis ECS-B-78, Rhizomucor pusillus ECS-710 and ECS-712, Aspergillus fumigatus ECS-709, and Thermomyces sp. ECS-711 were found to have a positive effect on A. bisporus mycelial growth.


2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Chiara Guerrieri ◽  
Andrea Fiorini ◽  
Elisabetta Fanfoni ◽  
Vincenzo Tabaglio ◽  
Pier Sandro Cocconcelli ◽  
...  

Plant growth promoting rhizobacteria (PGPR) can display several plant-beneficial properties, including support to plant nutrition, regulation of plant growth, and biocontrol of pests. Mechanisms behind these effects are directly related to the presence and expression of specific genes, and different PGPR strains can be differentiated by the presence of different genes. In this study we reported a comprehensive evaluation of a novel PGPR Klebsiella variicola UC4115 from the field to the lab, and from the lab to the plant. The isolate from tomato field was screened in-vitro for different activities related to plant nutrition and growth regulation as well as for antifungal traits. We performed a functional annotation of genes contributing to plant-beneficial functions previously tested in-vitro. Furthermore, the in-vitro characterization, the whole genome sequencing and annotation of K. variicola UC4115, were compared with the well-known PGPR Azospirillum brasilense strain Sp7. This novel comparative analysis revealed different accumulation of plant-beneficial functions contributing genes, and the presence of different genes that accomplished the same functions. Greenhouse assays on tomato seedlings from BBCH 11–12 to BBCH &gt; 14 were performed under either organic or conventional management. In each of them, three PGPR inoculations (control, K. variicola UC4115, A. brasilense Sp7) were applied at either seed-, root-, and seed plus root level. Results confirmed the PGP potential of K. variicola UC4115; in particular, its high value potential as indole-3-acetic acid producer was observed in increasing of root length density and diameter class length parameters. While, in general, A. brasilense Sp7 had a greater effect on biomass, probably due to its high ability as nitrogen-fixing bacteria. For K. variicola UC4115, the most consistent data were noticed under organic management, with application at seed level. While, A. brasilense Sp7 showed the greatest performance under conventional management. Our data highlight the necessity to tailor the selected PGPR, with the mode of inoculation and the crop-soil combination.


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