scholarly journals ROS amplification drives mouse spermatogonial stem cell self-renewal

2019 ◽  
Vol 2 (2) ◽  
pp. e201900374 ◽  
Author(s):  
Hiroko Morimoto ◽  
Mito Kanastu-Shinohara ◽  
Narumi Ogonuki ◽  
Satoshi Kamimura ◽  
Atsuo Ogura ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Nuclear Translocation ◽  
Cell Types ◽  
Spermatogonial Stem Cell ◽  
Self Renewal ◽  
Positive Feedback Loop ◽  
Chemical Screening

Reactive oxygen species (ROS) play critical roles in self-renewal division for various stem cell types. However, it remains unclear how ROS signals are integrated with self-renewal machinery. Here, we report that the MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via ROS amplification. The activation of MAPK14 induced MAPK7 phosphorylation in cultured SSCs, and targeted deletion of Mapk14 or Mapk7 resulted in significant SSC deficiency after spermatogonial transplantation. The activation of this signaling pathway not only induced Nox1 but also increased ROS levels. Chemical screening of MAPK7 targets revealed many ROS-dependent spermatogonial transcription factors, of which BCL6B was found to initiate ROS production by increasing Nox1 expression via ETV5-induced nuclear translocation. Because hydrogen peroxide or Nox1 transfection also induced BCL6B nuclear translocation, our results suggest that BCL6B initiates and amplifies ROS signals to activate ROS-dependent spermatogonial transcription factors by forming a positive feedback loop.

A negative feedback loop of transcription factors that controls stem cell pluripotency and self‐renewal

2006 ◽  
Vol 20 (10) ◽  
pp. 1730-1732 ◽  
Author(s):  
Guangjin Pan ◽  
Jun Li ◽  
Yali Zhou ◽  
Hui Zheng ◽  
Duanqing Pei ◽  
...  
Keyword(s):  
Stem Cell ◽  
Transcription Factors ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Self Renewal ◽  
Stem Cell Pluripotency

scholarly journals Targeting therapy-resistant lung cancer stem cells via disruption of the AKT/TSPYL5/PTEN positive-feedback loop

2020 ◽  
Author(s):  
In-Gyu Kim ◽  
Jei-Ha Lee ◽  
Seo-Yeon Kim ◽  
Chang-Kyu Heo ◽  
Rae-Kwon Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Transcriptional Activation ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Nuclear Translocation ◽  
Positive Feedback Loop ◽  
Targeting Therapy ◽  
Mesenchymal Transition

Abstract Cancer stem cells (CSCs) are regarded as essential targets to overcome tumor progression and therapeutic resistance; however, practical targeting approaches are limited. Here, we identify testis-specific Y-like protein 5 (TSPYL5) as a CSC-associated factor that promotes stemness and epithelial-to-mesenchymal transition in therapy-resistant non-small cell lung cancer (NSCLC) cells. Aberrantly activated PI3K/AKT pathway in therapy-resistant NSCLC cells promotes TSPYL5 phosphorylation at threonine-120 (pT120), which inhibits ubiquitination and stabilizes TSPYL5. TSPYL5 pT120 also supports SUMOylation, which leads to its nuclear translocation and functions as a transcriptional repressor of PTEN. Nuclear TSPYL5 also activates the transcription of CSC-associated genes, ALDH1 and CD44. Collectively, TSPYL5 pT120 maintains persistent CSC-like characteristics via transcriptional activation of CSC-associated genes and via a positive-feedback loop between the AKT/TSPYL5/PTEN and PTEN/PI3K/AKT signaling pathways. However, inhibition of TSPYL5 pT120 can block aberrant AKT/TSPYL5/PTEN cyclic signaling and cancer stemness. Our study suggests TSPYL5 as a novel target for cancer therapy.

scholarly journals Transcription Factors ER71/ETV2 and SOX9 Participate in a Positive Feedback Loop in Fetal and Adult Mouse Testis

2012 ◽  
Vol 287 (28) ◽  
pp. 23657-23666 ◽  
Author(s):  
Luciano DiTacchio ◽  
Josephine Bowles ◽  
Sook Shin ◽  
Dae-Sik Lim ◽  
Peter Koopman ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Adult Mouse ◽  
Mouse Testis ◽  
Positive Feedback Loop

scholarly journals MEF2C is a new regulator of the human articular chondrocyte phenotype

2018 ◽  
Author(s):  
S. Lazzarano ◽  
C.L. Murphy
Keyword(s):  
Transcription Factors ◽  
Articular Cartilage ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Regulator Gene ◽  
Articular Chondrocyte ◽  
Positive Feedback Loop ◽  
Chondrocyte Phenotype ◽  
Cooperative Activity ◽  
First Time

MEF2C plays a role in diverse tissues, most notably heart, brain, eyes and developing bones. Here we report for the first time that MEF2C is present and active in the permanent articular cartilage in humans which lines and protects our joints throughout life. We show that MEF2C directly targets cartilage master regulator gene SOX9, and SOX9, in turn, regulates MEF2C in a novel positive feedback loop maintaining high expression levels of both transcription factors, and consequently stabilising the articular chondrocyte phenotype and helping prevent hypertrophy and subsequent calcification and vascularisation. We propose that MEF2C and SOX9 may show similar cooperative activity in other tissues, and across a range of adult murine tissues we found co-expression of both transcription factors in cartilage, trachea, brain, eyes and heart. Strikingly, all of these tissues are prone to calcification and further study of MEF2C/SOX9 cooperativity in these organs will be revealing.

scholarly journals SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop

Gut ◽  
2017 ◽  
Vol 66 (12) ◽  
pp. 2149-2159 ◽  
Author(s):  
Chun-Ping Cui ◽  
Carmen Chak-Lui Wong ◽  
Alan Ka-Lun Kai ◽  
Daniel Wai-Hung Ho ◽  
Eunice Yuen-Ting Lau ◽  
...  
Keyword(s):  
Stem Cell ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Mrna Level ◽  
Cancer Stemness ◽  
Positive Feedback Loop ◽  
Sumo Proteases ◽  
Immunocompromised Mice ◽  
Element Sequence

ObjectiveWe investigated the effect and mechanism of hypoxic microenvironment and hypoxia-inducible factors (HIFs) on hepatocellular carcinoma (HCC) cancer stemness.DesignHCC cancer stemness was analysed by self-renewal ability, chemoresistance, expression of stemness-related genes and cancer stem cell (CSC) marker-positive cell population. Specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) mRNA level was examined with quantitative PCR in human paired HCCs. Immunoprecipitation was used to examine the binding of proteins and chromatin immunoprecipitation assay to detect the binding of HIFs with hypoxia response element sequence. In vivo characterisation was performed in immunocompromised mice and stem cell frequency was analysed.ResultsWe showed that hypoxia enhanced the stemness of HCC cells and hepatocarcinogenesis through enhancing HIF-1α deSUMOylation by SENP1 and increasing stabilisation and transcriptional activity of HIF-1α. Furthermore, we demonstrated that SENP1 is a direct target of HIF-1/2α and a previously unrecognised positive feedback loop exists between SENP1 and HIF-1α.ConclusionsTaken together, our findings suggest the significance of this positive feedback loop between HIF-1α and SENP1 in contributing to the increased cancer stemness in HCC and hepatocarcinogenesis under hypoxia. Drugs that specifically target SENP1 may offer a potential novel therapeutic approach for HCC.

scholarly journals Targeting therapy-resistant lung cancer stem cells via disruption of the AKT/TSPYL5/PTEN positive-feedback loop

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
In-Gyu Kim ◽  
Jei-Ha Lee ◽  
Seo-Yeon Kim ◽  
Chang-Kyu Heo ◽  
Rae-Kwon Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Transcriptional Activation ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Nuclear Translocation ◽  
Negative Regulator ◽  
Positive Feedback Loop ◽  
Targeting Therapy

AbstractCancer stem cells (CSCs) are regarded as essential targets to overcome tumor progression and therapeutic resistance; however, practical targeting approaches are limited. Here, we identify testis-specific Y-like protein 5 (TSPYL5) as an upstream regulator of CSC-associated genes in non-small cell lung cancer cells, and suggest as a therapeutic target for CSC elimination. TSPYL5 elevation is driven by AKT-dependent TSPYL5 phosphorylation at threonine-120 and stabilization via inhibiting its ubiquitination. TSPYL5-pT120 also induces nuclear translocation and functions as a transcriptional activator of CSC-associated genes, ALDH1 and CD44. Also, nuclear TSPYL5 suppresses the transcription of PTEN, a negative regulator of PI3K signaling. TSPYL5-pT120 maintains persistent CSC-like characteristics via transcriptional activation of CSC-associated genes and a positive feedback loop consisting of AKT/TSPYL5/PTEN signaling pathway. Accordingly, elimination of TSPYL5 by inhibiting TSPYL5-pT120 can block aberrant AKT/TSPYL5/PTEN cyclic signaling and TSPYL5-mediated cancer stemness regulation. Our study suggests TSPYL5 be an effective target for therapy-resistant cancer.

scholarly journals AP-1 Transcription Factors Mediate BDNF-Positive Feedback Loop in Cortical Neurons

2016 ◽  
Vol 36 (4) ◽  
pp. 1290-1305 ◽  
Author(s):  
J. Tuvikene ◽  
P. Pruunsild ◽  
E. Orav ◽  
E.-E. Esvald ◽  
T. Timmusk
Keyword(s):  
Transcription Factors ◽  
Positive Feedback ◽  
Cortical Neurons ◽  
Feedback Loop ◽  
Positive Feedback Loop
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