Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

myc oncogenes are transcription factors regulating the level of expression of other genes. Using a subtraction/coexpression strategy, a murine genetic target for Myc regulation was isolated. To further characterize this target gene, named ECA39, we have recently isolated the human, nematode and budding yeast homologs of the mouse gene. The recognition site for Myc binding, located 3' to the start site of transcription in the mouse gene, is conserved in the human homolog. Transfection experiments demonstrated that the Myc binding site of the human gene, mediates activation of a reporter gene in response to over-expression of c-myc. The activation was better executed when the c-Myc binding element was positioned downstream to the promoter, which is the usual position of the c-Myc DNA binding element in its genetic targets. The tissue specific expression of human ECA39 during embryogenesis is similar to that of the mouse homolog. Moreover, ECA39 is expressed in c-myc induced human tumors. It is expressed in Burkitt's lymphoma (where c-myc is translocated and activated) but not in non Burkitt's B-cell lymphoma or in T-cell lymphoma. Thus, it seems that ECA39 is a target for c-myc oncogenesis in humans. In yeast, where c-myc is absent, the ECA39 sequences lack the c-Myc binding element. However, the promoter region of the yeast ECA39 harbors several Gcn4 binding elements. Moreover, ECA39 is markedly down regulated in cells deleted for gcn4, and deletion of Gcn4 binding elements down regulated the transcription from ECA39 promoter. We thus suggest that ECA39 is a target for c-Myc regulation in mammals, while in yeast the regulator is not c-Myc but the c-Jun/c-Fos homolog - Gcn4.
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PMID:ECA39 is regulated by c-Myc in human and by a Jun/Fos homolog, Gcn4, in yeast. 893 31

Programmed cell death ligand 1 (PD-L1), inducing T cells exhaustion to facilitate immune escape of tumor cells, is up-regulated by interleukin 6 (IL-6) in T-Cell Lymphoma and ovarian cancer. The purpose of this study is to investigate the expression of IL-6 and PD-L1 in thyroid cancer, and whether IL-6 regulates the PD-L1 expression. As a result, IL-6 and PD-L1 were highly expressed in thyroid cancer tissues. Multivariate logistic analysis showed that tumor size, distant metastasis and risk stratification were significantly associated with IL-6 expression (p<0.05), and multifocality, lymph node metastasis, distant metastasis, risk stratification and IL-6 expression were identified as the independent predictors of PD-L1 expression (p<0.05). The invasiveness of thyroid cancer was significantly enhanced after IL-6 treatment or PD-L1 overexpression. PD-L1 positive rate correlated with IL6 expression in cancer tissues (p<0.001). And after IL-6 treatment, the PD-L1 expression in TPC-1 and BCPAP significantly increased. MAPK and JAK-STAT3 signaling pathways were activated by IL-6. And the IL-6-induced PD-L1 expression decreased after treatment of these two signaling pathway inhibitors. Knockdown of transcription factors c-Jun and stat3 suppressed the expression of PD-L1 induced by IL-6. And these two factors could bind to PD-L1 gene promoter directly and promote its transcription. It is concluded that IL-6 and PD-L1 are overexpressed in thyroid cancer and are related to tumor invasiveness. And IL-6 up-regulates PD-L1 expression through MAPK and JAK-STAT3 signaling pathway which function via transcription factors c-Jun and stat3.
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PMID:Interleukin 6 regulates the expression of programmed cell death ligand 1 in thyroid cancer. 3324 99