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

p130 Crk-associated substrate (Cas) is an adaptor protein associating with many other signaling proteins and regulates a various biological processes including cell adhesion, migration, and growth factor stimulation. However, the exact functional role of Cas in growth factor signaling pathway was poorly understood. Here we investigated the role of Cas and its domains in the effects of insulin, EGF, and IGF-1 on c-Jun gene expression, DNA synthesis, cytoskeletal reorganization. We found that microinjection of anti-Cas antibody and C-terminal domain of Cas (Cas-CT) specifically inhibited EGF-induced, but not insulin- or IGF-1-induced, c-Jun expression. Cell cycle progression and cytoskeleton reorganization induced by insulin and EGF, but not by IGF-1, were inhibited by microinjected anti-Cas and Cas-CT. In contrast, microinjection of the substate domain (Cas-SD) of Cas did not have any inhibitory effects. These results revealed that the Cas-CT is differentially implicated in insulin and EGF-mediated, but not IGF-1-mediated, c-Jun expression, DNA synthesis and membrane ruffling.
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PMID:Carboxy-terminal domain of Cas differentially modulates c-Jun expression, DNA synthesis, and membrane ruffling induced by insulin, EGF, and IGF-1. 3046 82

The programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) pathway plays a pivotal role in the immune escape of tumors. Many tumor cells show "glutamine dependence." However, the relationship between glutamine metabolism and PD-L1 expression has not been reported. In this study, changes in PD-L1 expression in renal carcinoma cells were evaluated during glutamine deprivation and recovery. Although PD-L1 expression differed in two renal cancer cell lines, both cell lines upregulated PD-L1 during glutamine deprivation, and the upregulated PD-L1 was restored to normal after glutamine recovery. Mechanistically, glutamine deprivation resulted in activation of EGFR signaling via ERKs 1 and 2 (ERK1/2) and c-Jun. In addition, treatment of renal cancer cells with EGF also induced PD-L1 expression and ERK1/2 phosphorylation. Finally, inhibitors of EGFR, ERK, and c-Jun all inhibited phosphorylation of c-Jun and downregulated PD-L1 expression induced by glutamine deprivation. Taken together, the data suggest that glutamine regulates the expression of PD-L1 through the EGFR/ERK/c-Jun pathway in renal cancer. IMPLICATIONS: This study reveals glutamine deprivation induces PD-L1 expression via activation of EGFR/ERK/c-Jun signaling in renal cancer and provides novel markers for the treatment of renal cancer.
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PMID:Glutamine Deprivation Induces PD-L1 Expression via Activation of EGFR/ERK/c-Jun Signaling in Renal Cancer. 3167 1

Multiple myeloma (MM) is one of the most common hematologic neoplastic diseases. Gossypol was once used as a male contraceptive but is considered a novel antitumor agent. This study aimed to reveal the gossypol-induced apoptosis mechanism and its hub genes. Gossypol-induced MM cell apoptosis is concentration- and time-dependent. Of a total of 532 differentially expressed genes, 273 genes were upregulated and 259 genes were downregulated in gossypol-treated MM cells. Through KEGG and WGCNA analyses, the apoptosis-associated module was identified, and JUN was identified as the hub gene. The expression of the JUN protein product c-Jun was downregulated in MM cell lines compared to that in normal plasma cells. High-risk MM patients had a lower expression of JUN. High-expression JUN group patients had a lower risk of death. JUN overexpression in MM cells induced potent cell death and growth inhibition by a caspase-dependent apoptotic mechanism. DR5 is one of the upstream receptors of the JNK pathway, and shRNA knockdown of DR5 can partially reverse gossypol-induced apoptosis. A total of 1017 genes were coexpressed with JUN in MM patients. These genes are mainly involved in other JNK-associated signaling pathways, such as the IL6, EGF and PDGF signaling pathways. In conclusion, JUN is identified as the hub gene in gossypol-induced apoptosis, and gossypol can activate caspase-dependent apoptosis through the JNK pathway by targeting c-Jun and other JNK-associated pathways. DR5 and IL6 are also involved in this mechanism.
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PMID:Gossypol induces apoptosis of multiple myeloma cells through the JUN-JNK pathway. 3226 96

Human papillomaviruses (HPV) are a major cause of malignancy worldwide, contributing to ~5% of all human cancers including almost all cases of cervical cancer and a growing number of ano-genital and oral cancers. HPV-induced malignancy is primarily driven by the viral oncogenes, E6 and E7, which manipulate host cellular pathways to increase cell proliferation and enhance cell survival, ultimately predisposing infected cells to malignant transformation. Consequently, a more detailed understanding of viral-host interactions in HPV-associated disease offers the potential to identify novel therapeutic targets. Here, we identify that the c-Jun N-terminal kinase (JNK) signalling pathway is activated in cervical disease and in cervical cancer. The HPV E6 oncogene induces JNK1/2 phosphorylation in a manner that requires the E6 PDZ binding motif. We show that blockade of JNK1/2 signalling using small molecule inhibitors, or knockdown of the canonical JNK substrate c-Jun, reduces cell proliferation and induces apoptosis in cervical cancer cells. We further demonstrate that this phenotype is at least partially driven by JNK-dependent activation of EGFR signalling via increased expression of EGFR and the EGFR ligands EGF and HB-EGF. JNK/c-Jun signalling promoted the invasive potential of cervical cancer cells and was required for the expression of the epithelial to mesenchymal transition (EMT)-associated transcription factor Slug and the mesenchymal marker Vimentin. Furthermore, JNK/c-Jun signalling is required for the constitutive expression of HPV E6 and E7, which are essential for cervical cancer cell growth and survival. Together, these data demonstrate a positive feedback loop between the EGFR signalling pathway and HPV E6/E7 expression, identifying a regulatory mechanism in which HPV drives EGFR signalling to promote proliferation, survival and EMT. Thus, our study has identified a novel therapeutic target that may be beneficial for the treatment of cervical cancer.
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PMID:E6-mediated activation of JNK drives EGFR signalling to promote proliferation and viral oncoprotein expression in cervical cancer. 3330 76


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