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Related Concept Videos

Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the addition of a...
Cell Signaling Feedback Loops01:07

Cell Signaling Feedback Loops

Positive and negative feedback loops are crucial for regulating biological signaling systems. These feedback loops are processes that connect output signals to their inputs.
Negative feedback loops
Most signaling systems have negative feedback loops that can perform different functions such as output limiter, and adaptation.
Output limiter
Upon receiving an input signal, the cellular response rapidly increases until a threshold is reached. Beyond this threshold, a negative feedback loop...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Regulation of Expression Occurs at Multiple Steps02:24

Regulation of Expression Occurs at Multiple Steps

Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
Transcription results in the generation of precursor (pre-mRNA) that consists of both exons and introns, which needs further processing before being translated to a...
Regulation of Food Intake01:30

Regulation of Food Intake

Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...

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Related Experiment Videos

FoxO1 mediates an autofeedback loop regulating SIRT1 expression.

Shiqin Xiong1, Gloria Salazar, Nikolay Patrushev

  • 1Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

The Journal of Biological Chemistry
|December 15, 2010
PubMed
Summary
This summary is machine-generated.

Forkhead transcription factor FoxO1 directly activates SIRT1 gene expression. SIRT1 also enhances FoxO1 activity, creating a positive feedback loop that regulates metabolism and aging.

Related Experiment Videos

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Forkhead transcription factor FoxO1 and SIRT1 are key regulators of aging, metabolism, and stress resistance.
  • SIRT1 deacetylates FoxO1, influencing its transcriptional activity.
  • The precise regulatory relationship between FoxO1 and SIRT1 is not fully understood.

Purpose of the Study:

  • To investigate the direct transcriptional regulation of SIRT1 by FoxO1.
  • To elucidate the feedback mechanisms between FoxO1 and SIRT1.

Main Methods:

  • Luciferase reporter assays to assess promoter activity.
  • Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) to confirm DNA binding.
  • siRNA-mediated gene silencing to determine the role of FoxO1 in SIRT1 expression.
  • Overexpression studies to validate findings.

Main Results:

  • FoxO1 directly binds to the rat SIRT1 promoter region, activating its transcription.
  • FoxO1 overexpression increases SIRT1 expression, while FoxO1 depletion reduces it.
  • SIRT1 deacetylates FoxO1, promoting a positive feedback loop for SIRT1 autotranscription.
  • Resveratrol, a SIRT1 activator, enhances FoxO1-dependent SIRT1 expression.

Conclusions:

  • Endogenous FoxO1 is a positive transcriptional regulator of SIRT1.
  • A positive feedback mechanism exists where SIRT1 enhances FoxO1-mediated SIRT1 transcription.
  • This FoxO1-SIRT1 signaling network plays a role in coordinating metabolic, inflammatory, and regenerative processes.