Myocardin-related transcription factors A and B (MRTFs) are coactivators of Serum Response Factor (SRF), which controls fundamental biological processes such as cell growth, migration, and differentiation. MRTF and SRF transcriptional activity play an important role in hepatocellular carcinoma (HCC) growth, which represents the second leading cause of cancer-related mortality in humans worldwide. We, therefore, searched for druggable targets in HCC that regulate MRTF/SRF transcriptional activity and can be exploited therapeutically for HCC therapy.
View Article and Find Full Text PDFIn cancer, the activating transcription factor 2 (ATF2) has pleiotropic functions in cellular responses to growth stimuli, damage, or inflammation. Due to only limited studies, the significance of ATF2 in colorectal cancer (CRC) is not well understood. We report that low ATF2 levels correlated with worse prognosis and tumor aggressiveness in CRC patients.
View Article and Find Full Text PDFAbnormalities of ventricular action potential cause malignant cardiac arrhythmias and sudden cardiac death. Here, we aim to identify microRNAs that regulate the human cardiac action potential and ask whether their manipulation allows for therapeutic modulation of action potential abnormalities. Quantitative analysis of the microRNA targetomes in human cardiac myocytes identifies miR-365 as a primary microRNA to regulate repolarizing ion channels.
View Article and Find Full Text PDFHuman hepatocellular carcinoma (HCC) is among the most lethal and common cancers in the human population, and new molecular targets for therapeutic intervention are urgently needed. Deleted in liver cancer 1 (DLC1) was originally identified as a tumor suppressor gene in human HCC. DLC1 is a Rho-GTPase-activating protein (RhoGAP) which accelerates the return of RhoGTPases to an inactive state.
View Article and Find Full Text PDFMyocardin-related transcription factors A and B (MRTFs) are coactivators of Serum Response Factor (SRF) that mediates the expression of genes involved in cell proliferation, migration and differentiation. There is mounting evidence that MRTFs and SRF represent promising targets for hepatocellular carcinoma (HCC) growth. Since MRTF-A nuclear localization is a prerequisite for its transcriptional activity and oncogenic properties, we searched for pharmacologically active compounds able to redistribute MRTF-A to the cytoplasm.
View Article and Find Full Text PDFOral Surg Oral Med Oral Pathol Oral Radiol
October 2016
Objective: In squamous cell carcinoma of the pharynx and larynx, NOTCH1 downstream signaling has been shown to be activated. The NOTCH1 signaling pathway has not been examined in detail for sinonasal squamous cell carcinomas (SNSCCs). The aim of this study was to evaluate NOTCH1 signaling by mRNA expression analysis and to examine the occurrence of NOTCH1 mutations in SNSCC.
View Article and Find Full Text PDFIn the recent years, the role of actin and actin-binding proteins in gene transcription has received considerable attention. Nuclear monomeric and polymerized actin and several actin binding proteins have been detected in the mammalian cell nucleus, although their roles in transcription are just beginning to emerge. Our group recently reported that the actin-binding protein Filamin A interacts with the transcriptional coactivator MKL1 to link actin polymerization with transcriptional activity of Serum Response Factor.
View Article and Find Full Text PDFThe expression of peptides and proteins as fusions to the B1 domain of streptococcal protein G (GB1) is very popular since GB1 often improves the solubility of the target protein and because the first purification step using IgG affinity chromatography is simple and efficient. However, the following protease digest is not always complete or can result in a digest of the target protein. In addition, a further purification step such as RP-HPLC has to be used to get rid of the GB1 tag and undigested fusion protein.
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