Signaling networks and transcription factors regulating mechanotransduction in bone

BioEssays ◽  
2009 ◽  
Vol 31 (7) ◽  
pp. 794-804 ◽  
Author(s):  
Dionysios J. Papachristou ◽  
Katerina K. Papachroni ◽  
Efthimia K. Basdra ◽  
Athanasios G. Papavassiliou
Keyword(s):  
Transcription Factors ◽  
Signaling Networks

scholarly journals Unraveling Melanin Biosynthesis and Signaling Networks in Cryptococcus neoformans

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Dongpil Lee ◽  
Eun-Ha Jang ◽  
Minjae Lee ◽  
Sun-Woo Kim ◽  
Yeonseon Lee ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cryptococcus Neoformans ◽  
Fungal Pathogens ◽  
Signaling Networks ◽  
Melanin Production ◽  
Nitrogen Base ◽  
Content Type ◽  
High Osmolarity ◽  
High Osmolarity Glycerol ◽  
The Core

ABSTRACT Melanin is an antioxidant polyphenol pigment required for the pathogenicity of many fungal pathogens, but comprehensive regulatory mechanisms remain unidentified. In this study, we systematically analyzed melanin-regulating signaling pathways in Cryptococcus neoformans and identified four melanin-regulating core transcription factors (TFs), Bzp4, Usv101, Mbs1, and Hob1, required for induction of the laccase gene (LAC1). Bzp4, Usv101, and Mbs1 independently regulate LAC1 induction, whereas Hob1 controls Bzp4 and Usv101 expression. Both Bzp4 and Usv101 are localized in the cytoplasm under nutrient-rich conditions (i.e., in the presence of yeast extract-peptone-dextrose [YPD] medium) but translocate into the nucleus upon nutrient starvation (i.e., in the presence of yeast nitrogen base [YNB] medium without glucose), and Mbs1 is constitutively localized in the nucleus. Notably, the cAMP pathway is not involved in regulation of the four TFs, but the high-osmolarity glycerol response (HOG) pathway negatively regulates induction of BZP4 and LAC1. Next, we searched for potential kinases upstream of the core TFs and identified nine core kinases; their deletion led to defective melanin production and LAC1 induction. Deletion of GSK3 or KIC1 abolished induction of LAC1 and BZP4 and perturbed nuclear translocation of Bzp4. Notably, Gsk3 also regulated expression of HOB1, USV101, and MBS1, indicating that it is a critical melanin-regulating kinase. Finally, an RNA sequencing-based transcriptome analysis of the wild-type strain and of bzp4Δ, usv101Δ, hob1Δ, and mbs1Δ strains under nutrient-rich and nutrient-starved conditions revealed that the melanin-regulating core TFs govern redundant and distinct classes of genes involved in a variety of biological processes. IMPORTANCE Melanins are dark green, brown, or black pigments that serve as antioxidant, reactive oxygen species (ROS) scavengers that protect fungal pathogens from radiation and host immune responses. Cryptococcus neoformans, the major etiological agent of fungal meningoencephalitis, also utilizes melanin as a key virulence factor. In this basidiomycete pathogen, melanin production is regulated by the cAMP and high-osmolarity glycerol response (HOG) pathways, and yet its complex signaling networks remain poorly described. In this study, we uncovered novel melanin synthesis regulatory networks consisting of core transcription factors (TFs), including Bzp4, Usv101, Hob1, and Mbs1, and core kinases Gsk3 and Kic1. These networks were identified through coupling systematic analyses of the expression and epistatic relationships of TF and kinase mutant libraries in the presence of diverse melanin substrates with transcriptome profiling of the core TF mutants. Thus, this report provides comprehensive insight into the melanin-regulating pathways in C. neoformans and other fungal pathogens.

scholarly journals Molecular mechanisms of epithelial to mesenchymal transition in tumor metastasis

2019 ◽  
Author(s):  
Artur Nieszporek ◽  
Klaudia Skrzypek ◽  
Grazyna Adamek ◽  
Marcin Majka
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Treatment Strategies ◽  
Cytoskeletal Proteins ◽  
Signaling Networks ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Growth Activation ◽  
Metastatic Sites

Epithelial to mesenchymal transition (EMT) is a process during which cancer cells lose epithelial features, cytoskeletal architecture is re-organized, cell shape changes and cells activate genes that help to define mesenchymal phenotype, what leads to an increased cell motility and dissemination of tumor to distant metastatic sites. This review describes different signaling networks between microRNAs and proteins that regulate EMT in tumor growth. Activation of EMT is mediated via series of paracrine signaling molecules. WNT, TGF-b, NOTCH and Shh signaling pathways play crucial roles in activation of EMT-related transcription factors, such as SNAIL, SLUG, ZEB1/2 or TWIST. Recent data provide evidence that crosstalk between microRNAs, long non-coding RNAs and EMT-transcription factors is crucial event in EMT regulation. MicroRNAs affect also level of proteins responsible for cellular contact, adhesion and cytoskeletal proteins, what induces changes of epithelial to mesenchymal phenotype. Understanding of those signaling networks may help to identify novel biomarkers or develop new treatment strategies based on microRNA therapeutics in future.

scholarly journals Characterization of Phototransduction Gene Knockouts Revealed Important Signaling Networks in the Light-Induced Retinal Degeneration

2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Jayalakshmi Krishnan ◽  
Gwang Lee ◽  
Sang-Uk Han ◽  
Sangdun Choi
Keyword(s):  
Transcription Factors ◽  
Late Phase ◽  
Signaling Networks ◽  
Neuronal Function ◽  
Double Knockout ◽  
Retinal Rod ◽  
Rhodopsin Kinase ◽  
Gene Knockouts ◽  
Chip Analysis

Understanding the molecular pathways mediating neuronal function in retinas can be greatly facilitated by the identification of genes regulated in the retinas of different mutants under various light conditions. We attempted to conduct a gene chip analysis study on the genes regulated during rhodopsin kinase (Rhok-/-) and arrestin (Sag-/-) knockout and double knockouts in mice retina. Hence, mice were exposed to constant illumination of 450 lux or 6,000 lux on dilated pupils for indicated periods. The retinas were removed after the exposure and processed for microarray analysis. Double knockout was associated with immense changes in gene expression regulating a number of apoptosis inducing transcription factors. Subsequently, network analysis revealed that during early exposure the transcription factors, p53, c-MYC, c-FOS, JUN, and, in late phase,NF-B, appeared to be essential for the initiation of light-induced retinal rod loss, and some other classical pro- and antipoptotic genes appeared to be significantly important as well.

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