scholarly journals The repression of nuclear factor I/CCAAT transcription factor (NFI/CTF) transactivating domain by oxidative stress is mediated by a critical cysteine (Cys-427)

2000 ◽  
Vol 348 (1) ◽  
pp. 235-240 ◽  
Author(s):  
Yannick MOREL ◽  
Robert BAROUKI
Keyword(s):  
Oxidative Stress ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Critical Role ◽  
Point Mutations ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Factor I ◽  
Nuclear Factor I

The activity of the nuclear factor I/CCAAT transcription factor (NFI/CTF) is negatively regulated by oxidative stress. The addition of relatively high (millimolar) H2O2 concentrations inactivates cellular NFI DNA-binding activity whereas lower concentrations can repress NFI/CTF transactivating function. We have investigated the mechanism of this regulation using Gal4 fusion proteins and transfection assays. We show that micromolar H2O2 concentrations repress the transactivating domain of NFI/CTF in a dose-dependent manner and are less or not active on other transcription factors' transactivating domains. Studies using deletions and point mutations pointed to the critical role of Cys-427. Indeed, when this cysteine is mutated into a serine, the repression by H2O2 is totally blunted. Mutation of other cysteine, serine and tyrosine residues within the transactivating domain had no clear effect on the repression by H2O2. Finally, treatment of cells with the thiol-alkylating reagent N-ethylmaleimide leads to a decrease in the transactivating function, which is dependent on Cys-427. This study shows that transactivating domains of transcription factors can constitute very sensitive targets of oxidative stress and highlights the critical role of these domains.

The Critical Role of Nuclear Factor I‐C in Tooth Development

Oral Diseases ◽  
2021 ◽  
Author(s):  
Chunmei Xu ◽  
Xudong Xie ◽  
Lei Zhao ◽  
Yafei Wu ◽  
Jun Wang
Keyword(s):  
Tooth Development ◽  
Critical Role ◽  
Nuclear Factor ◽  
Factor I ◽  
Nuclear Factor I

scholarly journals Nuclear factor I-C disrupts cellular homeostasis between autophagy and apoptosis via miR-200b-Ambra1 in neural tube defects

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wanqi Huang ◽  
Tianchu Huang ◽  
Yusi Liu ◽  
Jialin Fu ◽  
Xiaowei Wei ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Critical Role ◽  
Neural Tube Closure ◽  
Nuclear Factor ◽  
Cellular Homeostasis ◽  
Factor I ◽  
Nuclear Factor I ◽  
Insight Into

AbstractImpaired autophagy and excessive apoptosis disrupt cellular homeostasis and contribute to neural tube defects (NTDs), which are a group of fatal and disabling birth defects caused by the failure of neural tube closure during early embryonic development. However, the regulatory mechanisms underlying NTDs and outcomes remain elusive. Here, we report the role of the transcription factor nuclear factor I-C (NFIC) in maintaining cellular homeostasis in NTDs. We demonstrated that abnormally elevated levels of NFIC in a mouse model of NTDs can interact with the miR-200b promoter, leading to the activation of the transcription of miR-200b, which plays a critical role in NTD formation, as reported in our previous study. Furthermore, miR-200b represses autophagy and triggers apoptosis by directly targeting the autophagy-related gene Ambra1 (Autophagy/Beclin1 regulator 1). Notably, miR-200b inhibitors mitigate the unexpected effects of NFIC on autophagy and apoptosis. Collectively, these results indicate that the NFIC-miR-200b-Ambra1 axis, which integrates transcription- and epigenome-regulated miRNAs and an autophagy regulator, disrupts cellular homeostasis during the closure of the neural tube, and may provide new insight into NTD pathogenesis.

scholarly journals Thyroglobulin Repression of Thyroid Transcription Factor 1 (TTF-1) Gene Expression Is Mediated by Decreased DNA Binding of Nuclear Factor I Proteins Which Control Constitutive TTF-1 Expression

2000 ◽  
Vol 20 (22) ◽  
pp. 8499-8512 ◽  
Author(s):  
Minoru Nakazato ◽  
Hyun-Kyung Chung ◽  
Luca Ulianich ◽  
Antonino Grassadonia ◽  
Koichi Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Nuclear Factor ◽  
Factor I ◽  
Thyroid Transcription Factor 1 ◽  
Nuclear Extracts ◽  
Thyroid Transcription Factor ◽  
Nuclear Factor I ◽  
Transcription Factor 1

ABSTRACT Follicular thyroglobulin (TG) selectively suppresses the expression of thyroid-restricted transcription factors, thereby altering the expression of thyroid-specific proteins. In this study, we investigated the molecular mechanism by which TG suppresses the prototypic thyroid-restricted transcription factor, thyroid transcription factor 1 (TTF-1), in rat FRTL-5 thyrocytes. We show that the region between bp −264 and −153 on the TTF-1 promoter contains two nuclear factor I (NFI) elements whose function is involved in TG-mediated suppression. Thus, NFI binding to these elements is critical for constitutive expression of TTF-1; TG decreases NFI binding to the NFI elements in association with TG repression. NFI is a family of transcription factors that is ubiquitously expressed and contributes to constitutive and cell-specific gene expression. In contrast to the contribution of NFI proteins to constitutive gene expression in other systems, we demonstrate that follicular TG transcriptionally represses all NFI RNAs (NFI-A, -B, -C, and -X) in association with decreased NFI binding and that the RNA levels decrease as early as 4 h after TG treatment. Although TG treatment for 48 h results in a decrease in NFI protein-DNA complexes measured in DNA mobility shift assays, NFI proteins are still detectable by Western analysis. We show, however, that the binding of all NFI proteins is redox regulated. Thus, diamide treatment of nuclear extracts strongly reduces the binding of NFI proteins, and the addition of higher concentrations of dithiothreitol to nuclear extracts from TG-treated cells restores NFI-DNA binding to levels in extracts from untreated cells. We conclude that NFI binding to two NFI elements, at bp −264 to −153, positively regulates TTF-1 expression and controls constitutive TTF-1 levels. TG mediates the repression of TTF-1 gene expression by decreasing NFI RNA and protein levels, as well as by altering the binding activity of NFI, which is redox controlled.

scholarly journals Down Regulation of SIRT2 Reduced ASS Induced NSCLC Apoptosis Through the Release of Autophagy Components via Exosomes

2020 ◽  
Vol 8 ◽  
Author(s):  
Lei Wang ◽  
Pei Xu ◽  
Xiao Xie ◽  
Fengqing Hu ◽  
Lianyong Jiang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cell Apoptosis ◽  
Critical Role ◽  
Nsclc Cell ◽  
Dependent Manner ◽  
Cell Metastasis ◽  
Rna Immunoprecipitation ◽  
Transcription Factor Eb

Metastasis of cancer is the main cause of death in many types of cancer. Acute shear stress (ASS) is an important part of tumor micro-environment, it plays a crucial role in tumor invasion and spread. However, less is known about the role of ASS in tumorigenesis and metastasis of NSCLC. In this study, NSCLC cells were exposed to ASS (10 dyn/cm2) to explore the effect of ASS in regulation of autophagy and exosome mediated cell survival. Finally, the influence of SIRT2 on NSCLC cell metastasis was verified in vivo. Our data demonstrates that ASS promotes exosome and autophagy components releasing in a time dependent manner, inhibition of exosome release exacerbates ASS induced NSCLC cell apoptosis. Furthermore, we identified that this function was regulated by sirtuin 2 (SIRT2). And, RNA immunoprecipitation (RIP) assay suggested SIRT2 directly bound to the 3′UTR of transcription factor EB (TFEB) and facilitated its mRNA stability. TFEB is a key transcription factor involved in the regulation of many lysosome related genes and plays a critical role in the fusion of autophagosome and lysosome. Altogether, this data revealed that SIRT2 is a mechanical sensitive protein, and it regulates ASS induced cell apoptosis by modulating the release of exosomes and autophagy components, which provides a promising strategy for the treatment of NSCLCs.

scholarly journals Organization of the α-Globin Promoter and Possible Role of Nuclear Factor I in an α-Globin-inducible and in a Noninducible Cell Line

1995 ◽  
Vol 270 (33) ◽  
pp. 19643-19650 ◽  
Author(s):  
Theo Rein ◽  
Reinhold Förster ◽  
Anja Krause ◽  
Ernst-L. Winnacker ◽  
Haralabos Zorbas
Keyword(s):  
Cell Line ◽  
Nuclear Factor ◽  
Factor I ◽  
Nuclear Factor I ◽  
Globin Promoter
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