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Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-kB-dependent Signaling Pathway02:26

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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...

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Selectivity of the NF-{kappa}B response.

Ranjan Sen1, Stephen T Smale

  • 1Laboratory of Cellular and Molecular Biology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21225, USA. ranjan.sen@nih.gov <ranjan.sen@nih.gov>

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Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Immunology

Background:

  • Nuclear factor kappa B (NF-kappaB) is a crucial transcription factor activated by diverse stimuli.
  • NF-kappaB binding sites are present in numerous genes, indicating its broad regulatory role.
  • Despite its widespread involvement, NF-kappaB-dependent gene expression exhibits significant stimulus- and cell-type specificity.

Purpose of the Study:

  • To investigate the mechanistic framework underlying the stimulus- and cell-type-specific regulation of NF-kappaB-dependent gene expression.
  • To understand how different stimuli (e.g., TNFalpha, IL-1, LPS) elicit distinct cellular responses.
  • To elucidate the basis for differential gene expression in various cell types (e.g., lymphocytes, fibroblasts, epithelial cells) responding to the same NF-kappaB-inducing stimulus.
  • To account for the temporal dynamics (kinetics) of NF-kappaB-dependent gene activation.

Main Methods:

  • Analysis of regulatory mechanisms governing NF-kappaB signaling pathways.
  • Exploration of factors contributing to stimulus-specific gene activation.
  • Investigation of cell-type-specific responses mediated by NF-kappaB.
  • Examination of the temporal patterns of gene expression following NF-kappaB activation.

Main Results:

  • NF-kappaB-dependent gene expression is highly specific, varying with the inducing stimulus.
  • Different cell types display distinct transcriptional profiles in response to identical NF-kappaB activation.
  • The kinetics of gene expression are variable, with not all NF-kappaB-dependent genes being activated concurrently.
  • A mechanistic framework is proposed to explain these regulatory aspects.

Conclusions:

  • The specificity of NF-kappaB-dependent gene expression is achieved through complex regulatory mechanisms.
  • Understanding these mechanisms is vital for comprehending diverse physiological responses.
  • The framework presented provides a basis for analyzing stimulus- and cell-type-specific gene regulation by NF-kappaB.