Difference between revisions of "Part:BBa K4160005"

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<p><a href="https://2022.igem.wiki/tu-eindhoven/">TU-Eindhoven 2022</a> used this part as a transcription factor for the Generalized Extracellular Molecule Sensor (GEMS) system. Upon dimerization of the GEMS receptor (<a href="https://parts.igem.org/Part:BBa_K4160008">BBa_K4160008</a>), IL-6RB (<a href="https://parts.igem.org/Part:BBa_K4160002">BBa_K4160002</a>) domains are activated and induce downstream signaling of the JAK/STAT pathway, which results in STAT-induced gene expression.</p><br>
 
<p><a href="https://2022.igem.wiki/tu-eindhoven/">TU-Eindhoven 2022</a> used this part as a transcription factor for the Generalized Extracellular Molecule Sensor (GEMS) system. Upon dimerization of the GEMS receptor (<a href="https://parts.igem.org/Part:BBa_K4160008">BBa_K4160008</a>), IL-6RB (<a href="https://parts.igem.org/Part:BBa_K4160002">BBa_K4160002</a>) domains are activated and induce downstream signaling of the JAK/STAT pathway, which results in STAT-induced gene expression.</p><br>
  
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<h3>Characterization</h3>
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<h2>Characterization</h2>
 
<p>Characterization of STAT as the transcription factor in the GEMS system can be found on the <a href="https://parts.igem.org/Part:BBa_K4160008">BBa_K4160008</a> page.</p><br><br>
 
<p>Characterization of STAT as the transcription factor in the GEMS system can be found on the <a href="https://parts.igem.org/Part:BBa_K4160008">BBa_K4160008</a> page.</p><br><br>
  

Latest revision as of 14:16, 11 October 2022


STAT3 (Signal Transducer and Activator of Transcription 3)

Signal Transducer and Activator of Transcription 3 (STAT3) (Figure 1) is part of the STAT family. Phosphorylation of STAT3 leads to dimerization and activation of the STAT protein, which is important for mature hematopoietic cell production.1 In these cells, STAT proteins influence cellular survival, proliferation, and lineage-specific differentiation.1


Figure 1 | 3D structure of STAT3. (PDB: 6NUQ)2



Sequence and Features


Assembly Compatibility:
  • 10
    INCOMPATIBLE WITH RFC[10]
    Illegal EcoRI site found at 1226
    Illegal XbaI site found at 478
    Illegal PstI site found at 360
    Illegal PstI site found at 1221
    Illegal PstI site found at 2158
  • 12
    INCOMPATIBLE WITH RFC[12]
    Illegal EcoRI site found at 1226
    Illegal PstI site found at 360
    Illegal PstI site found at 1221
    Illegal PstI site found at 2158
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal EcoRI site found at 1226
    Illegal BglII site found at 565
    Illegal BamHI site found at 1145
  • 23
    INCOMPATIBLE WITH RFC[23]
    Illegal EcoRI site found at 1226
    Illegal XbaI site found at 478
    Illegal PstI site found at 360
    Illegal PstI site found at 1221
    Illegal PstI site found at 2158
  • 25
    INCOMPATIBLE WITH RFC[25]
    Illegal EcoRI site found at 1226
    Illegal XbaI site found at 478
    Illegal PstI site found at 360
    Illegal PstI site found at 1221
    Illegal PstI site found at 2158
  • 1000
    INCOMPATIBLE WITH RFC[1000]
    Illegal BsaI.rc site found at 1331
    Illegal BsaI.rc site found at 1370



Usage and Biology

STAT3 originates from Homo sapiens (human) and mediates cellular responses to interleukins and growth factors.2 The N-terminal domain of STAT proteins facilitates STAT oligomerization. This is important for increasing the stability and association with regulatory proteins.3 In addition, STAT contains a coiled-coil domain, that provides an anchoring domain for regulatory proteins, and a DNA-binding sequence that recognizes a specific DNA sequence, the STAT promotor (BBa_K4160006).3 Furthermore, STAT includes an SRC-homology 2 (SH2) domain, which is a transcriptional activation domain. This domain binds to phosphotyrosine (pY) residues of activated tyrosine kinases, which results in the phosphorylation of STAT proteins. In addition, SH2 domains contribute to the dimerization of STAT, which is essential for DNA binding.3


Activation of STAT

STAT3 is activated through receptor-associated kinase Janus Kinases (JAKs). Cellular responses, including growth factors or interleukins, interact with cytokine receptors on the cellular membrane. Consequently, these receptors will dimerize and induce activation of JAK proteins.3 Activated JAKs phosphorylate the cytokine receptors, which enables binding sites for the SH2 domains of STAT proteins.3 Inactivated STAT will be recruited and phosphorylated by tyrosine residues of the cytoplasmic region of the cytokine receptors. This phosphorylation results in the dimerization of STAT. Consequently, STAT will enter the nucleus and bind to the STAT promoter, which is located upstream of STAT target genes.3


GEMS system

TU-Eindhoven 2022 used this part as a transcription factor for the Generalized Extracellular Molecule Sensor (GEMS) system. Upon dimerization of the GEMS receptor (BBa_K4160008), IL-6RB (BBa_K4160002) domains are activated and induce downstream signaling of the JAK/STAT pathway, which results in STAT-induced gene expression.


Characterization

Characterization of STAT as the transcription factor in the GEMS system can be found on the BBa_K4160008 page.



References

  1. STAT Gene Family - Creative Biogene. Accessed October 11, 2022. https://www.creative-biogene.com/support/stat-gene-family.html
  2. STAT3 - Signal transducer and activator of transcription 3 - Homo sapiens (Human) | UniProtKB | UniProt. Accessed October 11, 2022. https://www.uniprot.org/uniprotkb/P40763/entry
  3. Lee DS, Grandis JR, Johnson DE. STAT3 as a Major Contributor to Chemoresistance. Target Cell Surviv Pathways to Enhanc Response to Chemother. Published online 2019:145-167. doi:10.1016/B978-0-12-813753-6.00007-X