scholarly journals A Creb3-Like Transcription Factor Coordinates ER Function upon Food Intake to Regulate Lipid Metabolism

2021 ◽  
Author(s):  
Haris A. Khan ◽  
Ming Toh ◽  
Tamás Schauer ◽  
Rory J. Beresford ◽  
Paula Ortega-Prieto ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Lipid Metabolism ◽  
Feeding Behavior ◽  
Transcriptional Activation ◽  
Feedback Loop ◽  
Protein Sorting ◽  
Nutrient Storage ◽  
Intracellular Organelle ◽  
Evolutionarily Conserved ◽  
Regulate Lipid Metabolism

SUMMARYIngestion of nutrients elicits essential physiological responses, including absorption, digestion, cessation of feeding and nutrient storage. The endoplasmic reticulum (ER) is central to this nutritional homeostasis, since it regulates intracellular organelle function, drives intercellular communication and promotes metabolite distribution. We identified theDrosophilaCreb3L-family transcription factor, CrebA, as the key metabolic regulator of ER function, thereby affecting lipid metabolism and feeding behavior. In response to feeding, CrebA activity is rapidly and transiently activated. CrebA directly drives the expression of the ER protein sorting machinery. We demonstrate that CrebA levels regulate lipid metabolism through lipoprotein secretion into the hemolymph and suppress feeding behavior. Further, CrebA mouse homologs are also upregulated in the liver following feeding and drive the transcriptional activation of ER protein sorting machinery genes in mammals. Our results reveal an evolutionarily conserved transcription switch which is turned on in response to food ingestion and orchestrates a negative feedback loop that promotes satiety by regulating ER function and protein secretion.

A Creb3L Transcription Factor Coordinates ER Function Upon Food Intake to Regulate Lipid Metabolism

2021 ◽  
Author(s):  
Haris A. Khan ◽  
Ming Toh ◽  
Sonja Mühlberger ◽  
Tamas Schauer ◽  
Rory J. Beresford ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Lipid Metabolism ◽  
Food Intake ◽  
Regulate Lipid Metabolism

Transcription factors important for starting the cell cycle in yeast

1993 ◽  
Vol 340 (1293) ◽  
pp. 351-360 ◽  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Dna Replication ◽  
Transcriptional Activation ◽  
Feedback Loop ◽  
Cell Cycle Progression ◽  
Regulatory Subunit ◽  
Cycle Progression ◽  
Embryonic Cleavage ◽  
Related Transcription Factor

Unlike early embryonic cleavage divisions in certain animals, cell-cycle progression in yeast and probably also in all metazoan somatic cells requires the periodic transcriptional activation of certain key genes. Thus far, the only clear examples are genes that encode a class of unstable ‘cyclin’ proteins, which bind and activate the cdc2/Cdc28 protein kinase: the G1-specific cyclins encoded by CLN1 and CLN2 , a B-type cyclin implicated in DNA replication encoded by CLB5 ; and four B-type cyclins involved in mitosis encoded by CLB1, 2, 3, 4. CLN1, CLN2 , and CLB5 are transcribed in late G1, as cells undergo Start. A transcription factor composed of Swi4 and Swi6 proteins (called SBF) activates CLN1 and CLN2 transcription via a positive feedback loop in which Cln proteins activate their own transcription. A different but related transcription factor called MBF seems responsible for the late G1-specific transcription of most DNA replication genes including CLB5 . We have purified MBF and shown that it contains Swi6 and a 110-120 kDa protein distinct from Swi4 (pl20) that contacts DNA. Thus, we propose that SBF and MBF share a common regulatory subunit (Swi6) but recognize their promoter elements via distinct DNA binding subunits.

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 Transcriptional Activation in Yeast Cells Lacking Transcription Factor IIA

Genetics ◽  
1999 ◽  
Vol 153 (4) ◽  
pp. 1573-1581 ◽  
Author(s):  
Susanna Chou ◽  
Sukalyan Chatterjee ◽  
Mark Lee ◽  
Kevin Struhl
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Large Subunit ◽  
Yeast Cells ◽  
Specific Cell ◽  
Wild Type ◽  
Activation Domains ◽  
Cycle Arrest ◽  
General Transcription Factor

Abstract The general transcription factor IIA (TFIIA) forms a complex with TFIID at the TATA promoter element, and it inhibits the function of several negative regulators of the TATA-binding protein (TBP) subunit of TFIID. Biochemical experiments suggest that TFIIA is important in the response to transcriptional activators because activation domains can interact with TFIIA, increase recruitment of TFIID and TFIIA to the promoter, and promote isomerization of the TFIID-TFIIA-TATA complex. Here, we describe a double-shut-off approach to deplete yeast cells of Toa1, the large subunit of TFIIA, to <1% of the wild-type level. Interestingly, such TFIIA-depleted cells are essentially unaffected for activation by heat shock factor, Ace1, and Gal4-VP16. However, depletion of TFIIA causes a general two- to threefold decrease of transcription from most yeast promoters and a specific cell-cycle arrest at the G2-M boundary. These results indicate that transcriptional activation in vivo can occur in the absence of TFIIA.

scholarly journals High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1740
Author(s):  
Yuning Pang ◽  
Xiang Xu ◽  
Xiaojun Xiang ◽  
Yongnan Li ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Fat Deposition ◽  
Liver Fat ◽  
Lipid Homeostasis ◽  
High Fat ◽  
Dual Inhibitor ◽  
Regulate Lipid Metabolism

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.

scholarly journals CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jin-Chun Qi ◽  
Zhan Yang ◽  
Tao Lin ◽  
Long Ma ◽  
Ya-Xuan Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transcriptional Activation ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Biological Effects ◽  
Therapeutic Benefit ◽  
Loss Of Function ◽  
Positive Feedback Loop

Abstract Background Both E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa. Methods The expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo. Results Here we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation. Conclusions These findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.

scholarly journals NAC Transcription Factor PwNAC11 Activates ERD1 by Interaction with ABF3 and DREB2A to Enhance Drought Tolerance in Transgenic Arabidopsis

2021 ◽  
Vol 22 (13) ◽  
pp. 6952
Author(s):  
Mingxin Yu ◽  
Junling Liu ◽  
Bingshuai Du ◽  
Mengjuan Zhang ◽  
Aibin Wang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Drought Stress ◽  
Stress Response ◽  
Transcriptional Activation ◽  
Dominant Role ◽  
State Level ◽  
Energy Conversion Efficiency ◽  
Nac Transcription Factor ◽  
Wild Plants ◽  
Transgenic Lines

NAC (NAM, ATAF1/2, and CUC2) transcription factors are ubiquitously distributed in eukaryotes and play significant roles in stress response. However, the functional verifications of NACs in Picea (P.) wilsonii remain largely uncharacterized. Here, we identified the NAC transcription factor PwNAC11 as a mediator of drought stress, which was significantly upregulated in P. wilsonii under drought and abscisic acid (ABA) treatments. Yeast two-hybrid assays showed that both the full length and C-terminal of PwNAC11 had transcriptional activation activity and PwNAC11 protein cannot form a homodimer by itself. Subcellular observation demonstrated that PwNAC11 protein was located in nucleus. The overexpression of PwNAC11 in Arabidopsis obviously improved the tolerance to drought stress but delayed flowering time under nonstress conditions. The steady-state level of antioxidant enzymes’ activities and light energy conversion efficiency were significantly increased in PwNAC11 transgenic lines under dehydration compared to wild plants. PwNAC11 transgenic lines showed hypersensitivity to ABA and PwNAC11 activated the expression of the downstream gene ERD1 by binding to ABA-responsive elements (ABREs) instead of drought-responsive elements (DREs). Genetic evidence demonstrated that PwNAC11 physically interacted with an ABA-induced protein—ABRE Binding Factor3 (ABF3)—and promoted the activation of ERD1 promoter, which implied an ABA-dependent signaling cascade controlled by PwNAC11. In addition, qRT-PCR and yeast assays showed that an ABA-independent gene—DREB2A—was also probably involved in PwNAC11-mediated drought stress response. Taken together, our results provide the evidence that PwNAC11 plays a dominant role in plants positively responding to early drought stress and ABF3 and DREB2A synergistically regulate the expression of ERD1.

Sign in / Sign up

Export Citation Format

Share Document