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Related Concept Videos

Translesion DNA Polymerases02:10

Translesion DNA Polymerases

Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
Thermosensation01:43

Thermosensation

Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
Repressible Operon: trp Operon01:21

Repressible Operon: trp Operon

The trp operon in Escherichia coli exemplifies a repressible operon. It regulates the synthesis of tryptophan through repressor-mediated transcriptional control and attenuation. This dual regulatory mechanism ensures tryptophan biosynthesis occurs only when needed, conserving cellular resources.Structure of the trp OperonThe trp operon consists of five structural genes (trpE, trpD, trpC, trpB, and trpA) that encode enzymes for tryptophan biosynthesis. These genes are transcribed as a single...
Transcription Attenuation in Prokaryotes02:42

Transcription Attenuation in Prokaryotes

Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure.  Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...

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Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
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TLR7 and TLR9 in SLE: when sensing self goes wrong.

T Celhar1, R Magalhães, A-M Fairhurst

  • 1Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, #03 Immunos, Singapore.

Immunologic Research
|March 22, 2012
PubMed
Summary

Regulatory mechanisms normally control autoreactive cells. In systemic lupus erythematosus (SLE), these cells expand, producing autoantibodies. Toll-like receptor (TLR) stimulation may contribute to SLE pathogenesis, with TLR7 potentially pathogenic and TLR9 protective.

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Area of Science:

  • Immunology
  • Autoimmunity
  • Molecular Biology

Background:

  • Autoreactive B and T cells are present in healthy individuals but regulated.
  • In systemic lupus erythematosus (SLE), autoreactive cells are expanded and activated, producing autoantibodies against nuclear antigens.
  • Immune complexes formed with self-nucleic acids and autoantibodies are characteristic of SLE.

Purpose of the Study:

  • To investigate the role of Toll-like receptor (TLR) stimulation in the aberrant adaptive immune response in SLE.
  • To explore the potential contribution of TLR7 and TLR9 signaling to SLE pathogenesis.

Main Methods:

  • Analysis of autoreactive cell behavior in SLE patients.
  • Investigation of immune complex formation with self-nucleic acids.
  • Assessment of TLR7 and TLR9 ligand activity in SLE serum.
  • Review of data from SLE mouse models.

Main Results:

  • Self-DNA and self-RNA can act as TLR9 and TLR7 ligands, respectively.
  • TLR stimulation is implicated as an additional factor in SLE immune response modulation.
  • Mouse models suggest TLR7 plays a pathogenic role, while TLR9 may be protective in SLE.

Conclusions:

  • TLR signaling pathways, specifically TLR7 and TLR9, are implicated in the complex pathogenesis of SLE.
  • Further research is required to fully elucidate the modulatory mechanisms and roles of TLR7 and TLR9 in human SLE.