scholarly journals The Oncogene Transcription Factor EB Regulates Vascular Functions

2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriella Doronzo ◽  
Elena Astanina ◽  
Federico Bussolino
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Leucine Zipper ◽  
Vascular System ◽  
Current Knowledge ◽  
Vascular Biology ◽  
Regulatory Role ◽  
Transcriptional Program ◽  
Transcription Factor Eb ◽  
Transcriptional Pathway

Transcription factor EB (TFEB) represents an emerging player in vascular biology. It belongs to the bHLH-leucine zipper transcription factor microphthalmia family, which includes microphthalmia-associated transcription factor, transcription factor E3 and transcription factor EC, and is known to be deregulated in cancer. The canonical transcriptional pathway orchestrated by TFEB adapts cells to stress in all kinds of tissues by supporting lysosomal and autophagosome biogenesis. However, emerging findings highlight that TFEB activates other genetic programs involved in cell proliferation, metabolism, inflammation and immunity. Here, we first summarize the general principles and mechanisms by which TFEB activates its transcriptional program. Then, we analyze the current knowledge of TFEB in the vascular system, placing particular emphasis on its regulatory role in angiogenesis and on the involvement of the vascular unit in inflammation and atherosclerosis.

scholarly journals Contribution of transcription factor EB to adipoRon-induced inhibition of arterial smooth muscle cell proliferation and migration

2019 ◽  
Vol 317 (5) ◽  
pp. C1034-C1047 ◽  
Author(s):  
Yun-Ting Wang ◽  
Jiajie Chen ◽  
Xiang Li ◽  
Michihisa Umetani ◽  
Yang Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Remodeling ◽  
Therapeutic Effects ◽  
Transcription Factor Eb ◽  
And Migration ◽  
Proliferation And Migration

Abnormal vascular smooth muscle cell (SMC) dedifferentiation with increased proliferation and migration during pathological vascular remodeling is associated with vascular disorders, such as atherosclerosis and in-stent restenosis. AdipoRon, a selective agonist of adiponectin receptor, has been shown to protect against vascular remodeling by preventing SMC dedifferentiation. However, the molecular mechanisms that mediate adipoRon-induced SMC differentiation are not well understood. The present study aimed to elucidate the role of transcription factor EB (TFEB), a master regulator of autophagy, in mediating adipoRon’s effect on SMCs. In cultured arterial SMCs, adipoRon dose-dependently increased TFEB activation, which is accompanied by upregulated transcription of genes involved in autophagy pathway and enhanced autophagic flux. In parallel, adipoRon suppressed serum-induced cell proliferation and caused cell cycle arrest. Moreover, adipoRon inhibited SMC migration as characterized by wound-healing retardation, F-actin reorganization, and matrix metalloproteinase-9 downregulation. These inhibitory effects of adipoRon on proliferation and migration were attenuated by TFEB gene silencing. Mechanistically, activation of TFEB by adipoRon is dependent on intracellular calcium, but it is not associated with changes in AMPK, ERK1/2, Akt, or molecular target of rapamycin complex 1 activation. Using ex vivo aortic explants, we demonstrated that adipoRon inhibited sprouts that had outgrown from aortic rings, whereas lentiviral TFEB shRNA transduction significantly reversed this effect of adipoRon on aortic rings. Taken together, our results indicate that adipoRon activates TFEB signaling that helps maintain the quiescent and differentiated status of arterial SMCs, preventing abnormal SMC dedifferentiation. This study provides novel mechanistic insights into understanding the therapeutic effects of adipoRon on TFEB signaling and pathological vascular remodeling.

scholarly journals The Regulatory Role of Activating Transcription Factor 2 in Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Tao Yu ◽  
Yong Jun Li ◽  
Ai Hong Bian ◽  
Hui Bin Zuo ◽  
Ti Wen Zhu ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Leucine Zipper ◽  
Regulatory Role ◽  
Neurological Development ◽  
Potential Applications ◽  
Inflammatory Drugs ◽  
Activating Transcription Factor ◽  
And Function ◽  
Potential Inhibitors

Activating transcription factor 2 (ATF2) is a member of the leucine zipper family of DNA-binding proteins and is widely distributed in tissues including the liver, lung, spleen, and kidney. Like c-Jun and c-Fos, ATF2 responds to stress-related stimuli and may thereby influence cell proliferation, inflammation, apoptosis, oncogenesis, neurological development and function, and skeletal remodeling. Recent studies clarify the regulatory role of ATF2 in inflammation and describe potential inhibitors of this protein. In this paper, we summarize the properties and functions of ATF2 and explore potential applications of ATF2 inhibitors as tools for research and for the development of immunosuppressive and anti-inflammatory drugs.

Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression

2005 ◽  
Vol 83 (4) ◽  
pp. 535-547 ◽  
Author(s):  
Gareth N Corry ◽  
D Alan Underhill
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Transcription Factors ◽  
Transcriptional Activation ◽  
Current Knowledge ◽  
Nuclear Architecture ◽  
Subnuclear Localization ◽  
Modular Structures

To date, the majority of the research regarding eukaryotic transcription factors has focused on characterizing their function primarily through in vitro methods. These studies have revealed that transcription factors are essentially modular structures, containing separate regions that participate in such activities as DNA binding, protein–protein interaction, and transcriptional activation or repression. To fully comprehend the behavior of a given transcription factor, however, these domains must be analyzed in the context of the entire protein, and in certain cases the context of a multiprotein complex. Furthermore, it must be appreciated that transcription factors function in the nucleus, where they must contend with a variety of factors, including the nuclear architecture, chromatin domains, chromosome territories, and cell-cycle-associated processes. Recent examinations of transcription factors in the nucleus have clarified the behavior of these proteins in vivo and have increased our understanding of how gene expression is regulated in eukaryotes. Here, we review the current knowledge regarding sequence-specific transcription factor compartmentalization within the nucleus and discuss its impact on the regulation of such processes as activation or repression of gene expression and interaction with coregulatory factors.Key words: transcription, subnuclear localization, chromatin, gene expression, nuclear architecture.

scholarly journals Mating Type in Chlamydomonas Is Specified by mid, the Minus-Dominance Gene

Genetics ◽  
1997 ◽  
Vol 146 (3) ◽  
pp. 859-869 ◽  
Author(s):  
Patrick J Ferris ◽  
Ursula W Goodenough
Keyword(s):  
Transcription Factor ◽  
Mating Type ◽  
Codon Bias ◽  
Leucine Zipper ◽  
Laboratory Strain ◽  
Leucine Zipper Motif ◽  
Type Locus ◽  
Diploid Cells ◽  
Necessary And Sufficient

Diploid cells of Chlamydomonas reinhardtii that are heterozygous at the mating-type locus (mt  +/mt  –) differentiate as minus gametes, a phenomenon known as minus dominance. We report the cloning and characterization of a gene that is necessary and sufficient to exert this minus dominance over the plus differentiation program. The gene, called mid, is located in the rearranged (R) domain of the mt  – locus, and has duplicated and transposed to an autosome in a laboratory strain. The imp11 mt  – mutant, which differentiates as a fusion-incompetent plus gamete, carries a point mutation in mid. Like the fus1 gene in the mt  + locus, mid displays low codon bias compared with other nuclear genes. The mid sequence carries a putative leucine zipper motif, suggesting that it functions as a transcription factor to switch on the minus program and switch off the plus program of gametic differentiation. This is the first sex-determination gene to be characterized in a green organism.

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