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Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

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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.
NF-κB-dependent Signaling Mechanism
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Co-activators and Co-repressors02:04

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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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Regulation of Nuclear Protein Sorting01:45

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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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Nuclear Export01:42

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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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Cells of the Innate Immune Response01:28

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The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
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The Intrinsic Apoptotic Pathway01:31

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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells
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Nuclear factor-kappaB: the enemy within.

Bharat B Aggarwal1

  • 1Cytokine Research Laboratory, Department of Experimental Therapeutics, Unit 143, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. aggarwal@mdanderson.org

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Nuclear factor NF-kappaB (NF-kappaB), a key inflammatory regulator, drives cancer development and progression. Inhibiting NF-kappaB activation offers a promising strategy for cancer prevention and treatment.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Nuclear factor NF-kappaB (NF-kappaB) is a proinflammatory transcription factor implicated in cancer.
  • NF-kappaB activation is triggered by inflammatory agents, carcinogens, tumor promoters, and the tumor microenvironment.

Purpose of the Study:

  • To review the role of NF-kappaB in promoting tumorigenesis.
  • To highlight the potential of NF-kappaB suppression in cancer therapy.

Main Methods:

  • Literature review of studies investigating NF-kappaB in cancer.
  • Analysis of NF-kappaB's involvement in key cancer hallmarks.

Main Results:

  • NF-kappaB and its regulated proteins are linked to cellular transformation, proliferation, apoptosis suppression, invasion, angiogenesis, and metastasis.
  • Constitutive NF-kappaB activation is prevalent in numerous tumors.
  • Genetic evidence supports NF-kappaB's role in mediating tumorigenesis.

Conclusions:

  • NF-kappaB plays a significant role in promoting cancer.
  • Targeting NF-kappaB activation presents a viable therapeutic strategy for cancer prevention and treatment.