Iranian Biomedical Journal
مجله بیومدیکال ایران
IBJ
Basic Sciences
http://ibj.pasteur.ac.ir
1
admin
1028-852X
2008-823X
-
10.61882/ibj
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8888
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en
jalali
1402
4
1
gregorian
2023
7
1
27
4
online
1
fulltext
en
Gαq Signaling Activates β-Catenin-Dependent Gene Transcription
Cancer Biology
Cancer Biology
مقاله کامل
Full Length/Original Article
<div style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:11pt"><span style="line-height:107%"><b><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">Background</span></span></span></b><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">: The canonical Wnt signal transduction or the Wnt/</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">β</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">-catenin pathway plays a crucial role in both carcinogenesis and development of animals. Activation of the G</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">q class of G</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black"> proteins positively regulates Wnt/</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">β</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">-catenin pathway, and expression of G</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">q in </span></span></span><span lang="EN-GB" style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">human embryonic kidney 293 (</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">HEK293T) cells or <i>Xenopus</i> oocytes leads to the inhibition of </span></span></span><span lang="EN-GB" style="font-size:10.5pt"><span style="line-height:107%">glycogen synthase kinase-3 beta</span></span> <span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">and cellular accumulation of </span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">β</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">-catenin. This study investigated whether G</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">q-mediated cellular accumulation of </span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">β-catenin could affect the transcriptional activity of this protein. </span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:107%"><b><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">Methods:</span></span></span></b><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black"> HEK-293T and HT-29 cells were used for cell culture and transfection. Protein localization and quantification were assessed by using immunofluorescence microscopy, cell fractionation assay, and Western blotting analysis. Gene expression at the transcription level was examined by quantitative reverse </span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">transcriptase/real-time PCR method.</span></span></span><span dir="RTL" lang="AR-SA" style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black"></span></span></span></span></span><br>
<span style="font-size:11pt"><span style="line-height:107%"><b><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">Results</span></span></span></b><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">: Transcription of two cellular </span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">β</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">-catenin target genes (<i>c-MYC </i>and <i>CCND1</i>) and the </span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">β</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">-catenin/</span></span></span><span lang="EN-GB" style="font-size:10.5pt"><span style="background:white"><span style="line-height:107%"><span style="color:#202124"> T-cell factor</span></span></span></span> <span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">reporter <i>luciferase</i> gene (TopFlash plasmid) significantly increased by G</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">q activation. The G</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">q-mediated increase in the expression level of the </span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">β</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">-catenin-target genes was sensitive to the expression of a minigene encoding a specific G</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">q blocking peptide. The results of cell fractionation and Western blotting experiments showed that activation of G</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">q signaling increased the intracellular </span></span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">β-catenin protein level, but it blocked its membrane localization.</span></span></span></span></span><br>
<b><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">Conclusion</span></span></span></b><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">: </span></span></span><span style="font-size:10.5pt"><span style="line-height:107%">Our results reveal that the G</span></span><span style="font-size:10.5pt"><span style="line-height:107%"><span style="color:black">α</span></span></span><span style="font-size:10.5pt"><span style="line-height:107%">q-dependent cellular accumulation of </span></span><span style="font-size:10.5pt"><span style="line-height:107%">β</span></span><span style="font-size:10.5pt"><span style="line-height:107%">-catenin can enhance </span></span><span style="font-size:10.5pt"><span style="line-height:107%">β</span></span><span style="font-size:10.5pt"><span style="line-height:107%">-catenin transcriptional activity.</span></span> </span></div>
β-catenin, Wnt signaling, G proteins
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http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-3459-3&slc_lang=en&sid=1
Sara
Ansari
ansari.sarabio@gmail.com