scholarly journals Role of a Putative Cyclic Di-GMP Forming Locus MSMEG_2196 in Mycobacterium Smegmatis

2021 ◽  
Author(s):  
◽  
Janet Youkhana
Keyword(s):  
Mycobacterium Smegmatis ◽  
Growth Conditions ◽  
Guanosine Monophosphate ◽  
Growth Effect ◽  
Altered Expression ◽  
Virulence Proteins ◽  
Cellular Processes ◽  
Colony Forming Units ◽  
Ggdef Domain

<p>Cyclic di-guanosine-monophosphate (c-di-GMP) has been recognized as a second messenger in bacteria controlling multiple cellular processes such as biofilm formation, motility, and virulence. Proteins containing GGDEF and EAL domains are engaged in the synthesis and degradation, respectively, of cyclic di-GMP. Some bacteria contain multiple proteins with GGDEF and EAL domains. The genome of Mycobacterium tuberculosis encodes only one protein (Rv1354c) which contains a GGDEF domain. This protein also contains a tandem EAL. The function of this protein in mycobacteria has not yet been determined. In this study, the orthologue of Rv1354c was investigated in Mycobacterium smegmatis (MSMEG_2196). The expression of MSMEG_2196 in M. smegmatis was altered by constructing sense and antisense expressing strains. The effect of the altered expression of MSMEG_2196 on M. smegmatis was tested under carbon, oxygen, phosphorous, and nitrogen limited growth conditions. There was no significant effect on growth in either the antisense or sense expressing strains grown under nutrient-rich, or carbon-, or oxygen-, or phosphorous limitation conditions. However, a growth effect was observed in the antisense expressing strain when grown under nitrogen-limited conditions. In particular, at mid stationary-phase (1,800 min) the MSMEG_2196 antisense strain had an OD600 value of 0.60, compared to that of the control M. smegmatis/pMind strain (OD600 value of 1.09). These results were further confirmed by the low colony forming units measures observed in MSMEG_2196 antisense strain. Proteomic analysis was carried out on the MSMEG_2196 antisesne expressing strain grown in the nitrogen-limited condition. Proteins that were differentially expressed were identified by mass spectrometry. A number of the proteins that were down-regulated in the antisense expressing strain are important in the survival of the bacteria under nitrogen-limited conditions. This study indicates a role for MSMEG_2196 in growth or survival of mycobacteria under nitrogen-limitations.</p>

scholarly journals Role of a Putative Cyclic Di-GMP Forming Locus MSMEG_2196 in Mycobacterium Smegmatis

2021 ◽  
Author(s):  
◽  
Janet Youkhana
Keyword(s):  
Mycobacterium Smegmatis ◽  
Growth Conditions ◽  
Guanosine Monophosphate ◽  
Growth Effect ◽  
Altered Expression ◽  
Virulence Proteins ◽  
Cellular Processes ◽  
Colony Forming Units ◽  
Ggdef Domain

<p>Cyclic di-guanosine-monophosphate (c-di-GMP) has been recognized as a second messenger in bacteria controlling multiple cellular processes such as biofilm formation, motility, and virulence. Proteins containing GGDEF and EAL domains are engaged in the synthesis and degradation, respectively, of cyclic di-GMP. Some bacteria contain multiple proteins with GGDEF and EAL domains. The genome of Mycobacterium tuberculosis encodes only one protein (Rv1354c) which contains a GGDEF domain. This protein also contains a tandem EAL. The function of this protein in mycobacteria has not yet been determined. In this study, the orthologue of Rv1354c was investigated in Mycobacterium smegmatis (MSMEG_2196). The expression of MSMEG_2196 in M. smegmatis was altered by constructing sense and antisense expressing strains. The effect of the altered expression of MSMEG_2196 on M. smegmatis was tested under carbon, oxygen, phosphorous, and nitrogen limited growth conditions. There was no significant effect on growth in either the antisense or sense expressing strains grown under nutrient-rich, or carbon-, or oxygen-, or phosphorous limitation conditions. However, a growth effect was observed in the antisense expressing strain when grown under nitrogen-limited conditions. In particular, at mid stationary-phase (1,800 min) the MSMEG_2196 antisense strain had an OD600 value of 0.60, compared to that of the control M. smegmatis/pMind strain (OD600 value of 1.09). These results were further confirmed by the low colony forming units measures observed in MSMEG_2196 antisense strain. Proteomic analysis was carried out on the MSMEG_2196 antisesne expressing strain grown in the nitrogen-limited condition. Proteins that were differentially expressed were identified by mass spectrometry. A number of the proteins that were down-regulated in the antisense expressing strain are important in the survival of the bacteria under nitrogen-limited conditions. This study indicates a role for MSMEG_2196 in growth or survival of mycobacteria under nitrogen-limitations.</p>

scholarly journals The dysregulated expression and functional effect of CaMK2 in cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qi He ◽  
Zhenyu Li
Keyword(s):  
Protein Kinase ◽  
Cancer Progression ◽  
Therapeutic Strategy ◽  
Altered Expression ◽  
Cellular Processes ◽  
Calcium Calmodulin Dependent ◽  
Specific Effects ◽  
Dependent Protein ◽  
Proliferation And Metastasis

AbstractCaMK2 (calcium/calmodulin-dependent protein kinase 2), a multifunctional serine/threonine-protein kinase involved in diverse cellular processes, is vital for the transduction of the Ca2+ signaling cascade. Recently, research has highlighted the involvement of CaMK2 in cancer development. However, the specific effects of CaMK2 on cancer have not been fully elucidated. In this review, we summarize not only the altered expression of CaMK2 in a range of cancers, as evidenced by bioinformatics analysis, but also the significant role of CaMK2 in regulating cancer progression, such as proliferation and metastasis. In addition, we described the functional influence of CaMK2 on cancer stemness and resistance. Understanding the critical effects and mechanisms of CaMK2 in cancer would facilitate the development of a promising therapeutic strategy for cancer treatment.

scholarly journals Proximity interactome of LC3B in normal growth conditions

2021 ◽  
Author(s):  
Marie Nollet ◽  
Alexander Agrotis ◽  
Fanourios Michailidis ◽  
Arran David Dokal ◽  
Vinothini Rajeeve ◽  
...  
Keyword(s):  
Cell Biology ◽  
Normal Growth ◽  
Growth Conditions ◽  
Biological Functions ◽  
Normal Medium ◽  
Outer Membranes ◽  
Cellular Processes ◽  
Proteomic Approach ◽  
And Function

LC3 (Light Chain 3) is a key player of autophagy, a major stress-responsive proteolysis pathway promoting cellular homeostasis. It coordinates the formation and maturation of autophagosomes and recruits cargo to be further degraded upon autophagosome-lysosome fusion. To orchestrate its functions, LC3 binds to multiple proteins from the autophagosomes inner and outer membranes, but the full extent of these interactions is not known. Moreover, LC3 has been increasingly reported in other cellular locations than the autophagosome, with cellular outcome not fully understood and not all related to autophagy. Furthermore, novel functions of LC3 as well as autophagy can occur in cells growing in a normal medium thus in non-stressed conditions. A better knowledge of the molecule in proximity to LC3 in normal growth conditions will improve the understanding of LC3 function in autophagy and in other cell biology function. Using an APEX2 based proteomic approach, we have detected 407 proteins in proximity to the well-characterised LC3B isoform in non-stress conditions. These include known and novel LC3B proximity proteins, associated with various cell localisation and biological functions. Sixty-nine of these proteins contain a putative LIR (LC3 Interacting Region) including 41 not reported associated to autophagy. Several APEX2 hits were validated by co-immunoprecipitation and co-immunofluorescence. This study uncovers the LC3B global interactome and reveals novel LC3B interactors, irrespective of LC3B localisation and function. This knowledge could be exploited to better understand the role of LC3B in autophagy and non-autophagy cellular processes.

Ion channels and transporters in cancer. 4. Remodeling of Ca2+ signaling in tumorigenesis: role of Ca2+ transport

2011 ◽  
Vol 301 (5) ◽  
pp. C969-C976 ◽  
Author(s):  
Jane M. Lee ◽  
Felicity M. Davis ◽  
Sarah J. Roberts-Thomson ◽  
Gregory R. Monteith
Keyword(s):  
Ion Channels ◽  
Tumor Formation ◽  
Altered Expression ◽  
Present Evidence ◽  
Cellular Processes ◽  
New Evidence

The Ca2+ signal has major roles in cellular processes important in tumorigenesis, including migration, invasion, proliferation, and apoptotic sensitivity. New evidence has revealed that, aside from altered expression and effects on global cytosolic free Ca2+ levels via direct transport of Ca2+, some Ca2+ pumps and channels are able to contribute to tumorigenesis via mechanisms that are independent of their ability to transport Ca2+ or effect global Ca2+ homeostasis in the cytoplasm. Here, we review some of the most recent studies that present evidence of altered Ca2+ channel or pump expression in tumorigenesis and discuss the importance and complexity of localized Ca2+ signaling in events critical for tumor formation.

scholarly journals Oncogenic Role of miRNA in Environmental Exposure to Plasticizers: A Systematic Review

2021 ◽  
Vol 11 (6) ◽  
pp. 500
Author(s):  
Margherita Ferrante ◽  
Antonio Cristaldi ◽  
Gea Oliveri Conti
Keyword(s):  
Systematic Review ◽  
Environmental Exposure ◽  
Environmental Pollutants ◽  
Altered Expression ◽  
Toxicological Assessment ◽  
Cellular Processes ◽  
Global Issue ◽  
Meta Analyses ◽  
The Relationship

The daily environmental exposure of humans to plasticizers may adversely affect human health, representing a global issue. The altered expression of microRNAs (miRNAs) plays an important pathogenic role in exposure to plasticizers. This systematic review summarizes recent findings showing the modified expression of miRNAs in cancer due to exposure to plasticizers. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, we performed a systematic review of the literature published in the past 10 years, focusing on the relationship between plasticizer exposure and the expression of miRNAs related to cancer. Starting with 535 records, 17 articles were included. The results support the hypothesis that exposure to plasticizers causes changes in or the deregulation of a number of oncogenic miRNAs and show that the interaction of plasticizers with several redundant miRNAs, such as let-7f, let-7g, miR-125b, miR-134, miR-146a, miR-22, miR-192, miR-222, miR-26a, miR-26b, miR-27b, miR-296, miR-324, miR-335, miR-122, miR-23b, miR-200, miR-29a, and miR-21, might induce deep alterations. These genotoxic and oncogenic responses can eventually lead to abnormal cell signaling pathways and metabolic changes that participate in many overlapping cellular processes, and the evaluation of miRNA-level changes can be a useful target for the toxicological assessment of environmental pollutants, including plastic additives and plasticizers.

The NAD Kinase Slr0400 Functions as a Growth Repressor in Synechocystis sp. PCC 6803

2021 ◽  
Author(s):  
Yuuma Ishikawa ◽  
Cedric Cassan ◽  
Aikeranmu Kadeer ◽  
Koki Yuasa ◽  
Nozomu Sato ◽  
...  
Keyword(s):  
Constitutive Expression ◽  
Physiological Role ◽  
Tca Cycle ◽  
Growth Conditions ◽  
Deficient Mutant ◽  
Nad Kinase ◽  
Cellular Processes ◽  
The Tca Cycle ◽  
Living Organisms

Abstract NADP+, the phosphorylated form of nicotinamide adenine dinucleotide (NAD), plays an essential role in many cellular processes. NAD kinase (NADK), which is conserved in all living organisms, catalyzes the phosphorylation of NAD+ to NADP+. However, the physiological role of phosphorylation of NAD+ to NADP+ in the cyanobacterium Synechocystis remains unclear. In this study, we report that slr0400, an NADK-encoding gene in Synechocystis, functions as a growth repressor under light-activated heterotrophic growth conditions and light and dark cycle conditions in the presence of glucose. We show, via characterization of NAD(P)(H) content and enzyme activity, that NAD+ accumulation in slr0400-deficient mutant results in the unsuppressed activity of glycolysis and tricarboxylic acid (TCA) cycle enzymes. In determining whether Slr0400 functions as a typical NADK, we found that constitutive expression of slr0400 in an Arabidopsis nadk2-mutant background complements the pale-green phenotype. Moreover, to determine the physiological background behind the growth advantage of mutants lacking slr04000, we investigated the photobleaching phenotype of slr0400-deficient mutant under high-light conditions. Photosynthetic analysis found in the slr0400-deficient mutant resulted from malfunctions in the Photosystem II (PSII) photosynthetic machinery. Overall, our results suggest that NADP(H)/NAD(H) maintenance by slr0400 plays a significant role in modulating glycolysis and the TCA cycle to repress the growth rate and maintain the photosynthetic capacity.

scholarly journals Oncogenic Role of miRNA by Environmental Exposure to Plasticizers: A Systematic Review.

2021 ◽  
Author(s):  
Margherita Ferrante ◽  
Antonio Cristaldi ◽  
Gea Oliveri Conti
Keyword(s):  
Systematic Review ◽  
Environmental Exposure ◽  
Environmental Pollutants ◽  
Altered Expression ◽  
Toxicological Assessment ◽  
Cellular Processes ◽  
Global Issue ◽  
Meta Analyses ◽  
The Relationship

The environmental exposure of human in the daily and occupational activities to plasticizers may adversely affect human health, and thus represents a global issue. The altered expression of MicroRNAs (miRNAs) exerts an important pathogenic role linked also to the exposure to plasticizers. This systematic review summarizes the recent findings showing modified ex-pression of miRNAs in cancer due to plasticizers exposures. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, we performed a systematic review of the past ten years, focusing on the relationship between plasticizer exposures and expression of miRNAs cancer. Starting by 535 records, 17 articles were included. Results support the hypothesis that exposure to plasticizers cause changes or deregulation of a number of oncogenic miRNAs and showed that plasticizers interaction with several redundant miRNAs, such as let-7f, let-7g, miR-125b, miR-134, miR-146a, miR-22; miR-192, miR-222, miR-26a, miR-26b, miR-27b, miR-296, miR-324, miR-335, miR-122, miR-23b, miR-200, miR-29a and miR-21, might induce deep alterations. These genotoxic and oncogenic responses can eventually lead to abnormal cell signaling pathways and metabolisms that participate in many overlapped cellular processes, and miRNA level changes can be a useful tool for the toxicological assessment of environmental pollutants, including plastic additives and plasticizers

scholarly journals Integration of Clinical and Transcriptomics Reveals Reprogramming of the Lipid Metabolism in Gastric Cancer

2021 ◽  
Author(s):  
Yanyan Li ◽  
Jungang Zhao ◽  
Renpin Chen ◽  
Shengwei Chen ◽  
Yilun Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lipid Metabolism ◽  
Cox Regression ◽  
Gene Signature ◽  
Cancer Cell Proliferation ◽  
Related Gene ◽  
Altered Expression ◽  
Transcriptomic Data ◽  
Cellular Processes

Abstract Background: Lipid metabolism has a profound impact on gastric cancer (GC) progression and is a newly targetable vulnerability for cancer therapy. Given the importance of lipids in cancer cellular processes, in this study we employed lipidomic clinical and transcriptomic data of GC to connect the variations of lipid metabolism changes.Method: We constructed a clinical nomogram based on the lipid factors and other clinical items. Then by using multi-omics techniques, we established a lipid-related gene signature for individualized prognosis prediction in patients with GC. Moreover, a total of 1357 GC cases were then applied to evaluate the robustness of this model. WGCNA was used to identify co-expression modules and enriched genes associated with GC lipid metabolism. The role of key genes ACLY in GC was further investigated.Results: The prognostic value of the lipidomic signature was analyzed using Cox regression model, and clinical nomogram was established. Among them, we observed overexpression of ACLY significantly increased the levels of intracellular free fatty acid and triglyceride, and activate AKT/mTOR pathway to promote cancer development.Conclusions: In conclusion, our findings delineated a GC clinical and lipidomic signature and revealed that GC exhibited a reprogramming of lipid metabolism in association with an altered expression of lipid metabolism-associated genes. Among them, ACLY significantly promoted GC lipid metabolism and increased cancer cell proliferation, suggesting that this pathway can be targetable as a metabolic vulnerability in future GC therapy.

scholarly journals Cdc48-like protein of actinobacteria (Cpa) is a novel proteasome interactor in mycobacteria and related organisms

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Michal Ziemski ◽  
Ahmad Jomaa ◽  
Daniel Mayer ◽  
Sonja Rutz ◽  
Christoph Giese ◽  
...  
Keyword(s):  
Mycobacterium Smegmatis ◽  
Ribosomal Proteins ◽  
Essential Role ◽  
Eukaryotic Cells ◽  
Wild Type ◽  
Core Particle ◽  
Oligomeric State ◽  
Aaa Atpase ◽  
Cellular Processes

Cdc48 is a AAA+ ATPase that plays an essential role for many cellular processes in eukaryotic cells. An archaeal homologue of this highly conserved enzyme was shown to directly interact with the 20S proteasome. Here, we analyze the occurrence and phylogeny of a Cdc48 homologue in Actinobacteria and assess its cellular function and possible interaction with the bacterial proteasome. Our data demonstrate that Cdc48-like protein of actinobacteria (Cpa) forms hexameric rings and that the oligomeric state correlates directly with the ATPase activity. Furthermore, we show that the assembled Cpa rings can physically interact with the 20S core particle. Comparison of the Mycobacterium smegmatis wild-type with a cpa knockout strain under carbon starvation uncovers significant changes in the levels of around 500 proteins. Pathway mapping of the observed pattern of changes identifies ribosomal proteins as a particular hotspot, pointing amongst others toward a role of Cpa in ribosome adaptation during starvation.

scholarly journals The Critical Role of embC in Mycobacterium tuberculosis

2008 ◽  
Vol 190 (12) ◽  
pp. 4335-4341 ◽  
Author(s):  
Renan Goude ◽  
Anita G. Amin ◽  
Delphi Chatterjee ◽  
Tanya Parish
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Smegmatis ◽  
Essential Gene ◽  
Critical Role ◽  
Normal Growth ◽  
Growth Conditions ◽  
Northern Analysis ◽  
Immunomodulatory Effects ◽  
Key Genes

ABSTRACT Arabinan polymers are major components of the cell wall in Mycobacterium tuberculosis and are involved in maintaining its structure, as well as playing a role in host-pathogen interactions. In particular, lipoarabinomannan (LAM) has multiple immunomodulatory effects. In the nonpathogenic species Mycobacterium smegmatis, EmbC has been identified as a key arabinosyltransferase involved in the incorporation of arabinose into LAM, and an embC mutant is viable but lacks LAM. In contrast, we demonstrate here that in M. tuberculosis, embC is an essential gene under normal growth conditions, suggesting a more crucial role for LAM in the pathogenic mycobacteria. M. tuberculosis EmbC has an activity similar to that of M. smegmatis EmbC, since we were able to complement an embC mutant of M. smegmatis with embCMtb , confirming that it encodes a functional arabinosyltransferase. In addition, we observed that the size of LAM produced in M. smegmatis was dependent on the level of expression of embCMtb . Northern analysis revealed that embC is expressed as part of a polycistronic message encompassing embC and three upstream genes. The promoter region for this transcript was identified and found to be up-regulated in stationary phase but down-regulated during hypoxia-induced nonreplicating persistence. In conclusion, we have identified one of the key genes involved in LAM biosynthesis in M. tuberculosis and confirmed its essential role in this species.

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