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STAT3Signal Transducer and Activator of Transcription 3 (gene)
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Klemp concluded: 'Notwithstanding the relatively rare nature of CTCL, we believe showing activity with one of our STAT3 inhibitors, within our WP1066 family of molecules, could be an indicator of both the value of p-STAT3 as a target and the potential for our drugs in other cancers where STAT3 is highly activated.'
A mutation in signal transducer and activator of transcription 3 (STAT3) is responsible for autosomal dominant hyper IgE syndrome, a rare and primary cellular complex disorder linked to mutation in the gene encoding for signal transduction STAT33.
Brave nine-year-old Michael Beazley, from Kerry in Ireland, also suffers from a STAT3 gene mutation.
Fortunately, he was offered a DNA test and it was then we found out he had a STAT3 gene mutation, meaning that the auto-immunity could affect his organs.
"Soon after he was diagnosed with STAT 3 GOF -- the same condition Lilly had -- even though he showed different symptoms." Brave nine-year-old Michael Beazley, from Kerry in Ireland, also suffers from a STAT3 gene mutation.
In the study, the scientists used mouse models to demonstrate that Stat3 promotes mitochondrial respiration.
HULC: Highly up-regulated in liver cancer; FOXM1: forkhead box protein M1; NC: negative control; PI3K: phosphatidylinositol 3-kinase; AKT: protein kinase 3; mTOR: mammalian target of rapamycin; JAK1: janus kinase 1; STAT3: signal transducing activator of transcription 3.
The anti-metastatic activity of BHS-I was found to be associated with inhibition of STAT3 activation at tyrosine705 (Tyr705), decreased expression of COX-2, MMP-2, MMP-9, and N-cadherin and increased expression of E-cadherin.
The preliminary studies of the project showed that the siRNA targeting to STAT3 (target sequence: CCGTGGAACCATACACAAA, sense: 5'- CCGUGGAACCAUACACAAAdTdT-3' and antisense: 3'- dTdTGGCACCUUGGUAUGUGUUU-5') achieved the highest knockdown effect among three designed siRNAs and was selected for the following experiments.
As the Signal Transducer and Activator of Transcription 3 (STAT3) pathway has widely been reported to modulate inflammation and proliferation, we further noted that STAT3 phosphorylation was increased 2.3-fold in BDL rats compared with the sham rats (P < 0.01) and total STAT3 protein levels increased by 1.5-fold (P < 0.05).
Antibodies against GAPDH, PCNA, AKT, p-AKT, Bcl2, Bcl-xl, STAT3, pSTAT3, FASN, and Cyclin D1 were purchased from Abcam.
Among the STAT3 gene mutations in literature for AD-HIES, V463E variant of STAT3 gene with a "loss of function" (located at the DNA-binding domain), found in our patient, has neither been published as a pathogenic nor been a benign variant to our knowledge.