The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

Hartl, Markus; Puglisi, Kane; Nist, Andrea; Raffeiner, Philipp; Bister, Klaus

doi:10.1002/1878-0261.12636

Cited by 21 publications

(20 citation statements)

References 69 publications

(187 reference statements)

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“…Primary quail embryo fibroblasts (QEF) were prepared from 9-d old fertilized quail eggs and cells cultivated as described (32). Calcium phosphate-mediated transfection of DNA into fibroblasts and quantification of cell transformation by focus formation were performed as described (33,34). Cultivation and DNA transfection of human epithelial kidney cells (HEK-293T) by lipofection have been described (35).…”

Section: Cell Culture and Cell Transformation Assaymentioning

confidence: 99%

“…The pRc/RSV-derived eukaryotic expression vectors pRc-HA-v-Myc and pRc-v-Src have been described (34). Transcriptional transactivation analysis using the luciferase reporter system, including the firefly luciferase constructs pGL3-WS5 (pLUC-WS5) and the empty vector pGL3-Basic (pLUC), has been described (33,34,36). The eukaryotic expression construct pcDNA3.1-Rluc used for constitutive renilla luciferase expression, and the empty pcDNA3.1 vector have been described (34).…”

Section: Expression Plasmids Gene Transfer Reporter Gene Assay and Cell Proliferation Analysismentioning

confidence: 99%

“…The eukaryotic expression construct pcDNA3.1-Rluc used for constitutive renilla luciferase expression, and the empty pcDNA3.1 vector have been described (34). Proliferation of cells treated with curcumin (CRM) was monitored in real time by using the live cell imaging system IncuCyte S3 (Essen Bioscience/Sartorius, Vienna, Austria) as described (33). Cells were seeded in a 24well dish (Corning, Vienna, Austria), and incubated overnight.…”

Section: Expression Plasmids Gene Transfer Reporter Gene Assay and Cell Proliferation Analysismentioning

confidence: 99%

“…The c-myc gene (MYC) has been originally identified as transduced viral allele termed v-myc in the transforming avian acute leukemia virus MC29 (3,38). To test for oncogenic MYC activity we consequently used an original avian cell system and the retroviral RCAS expression vector (33). The v-myc gene fused at its N-terminus with a hemagglutinin (HA) tag was overexpressed in primary quail embryo fibroblast (QEF) and cell transformation monitored in a focus assay, where clonal microtumors result from single transformation events.…”

Section: Curcumin Inhibits Myc-specific Cell Transformationmentioning

confidence: 99%

“…To test if curcumin also affects this central MYC function, a firefly luciferase reporter plasmid (pLUC-WS5) containing the promoter from the MYC-specific target gene WS5 (33, 39) was transfected into human embryonal kidney cells (HEK293T) representing a suitable cell system to monitor transcriptional promoter activities (35) (Figure 2). These cells, which express endogenous MYC at high levels (33) were treated without or with curcumin. Whereas in untreated cells, the WS5 promoter was efficiently transactivated by the endogenous MYC protein as expected, increasing curcumin concentrations led to a significant reduction in luciferase activities (Figure 2B).…”

Section: Curcumin Interferes With Transcriptional Activation Of Mycmentioning

confidence: 99%

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The Diarylheptanoid Curcumin Induces MYC Inhibition and Cross-Links This Oncoprotein to the Coactivator TRRAP

et al. 2021

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The c-Myc protein (MYC) is a transcription factor with strong oncogenic potential controlling fundamental cellular processes. In most human tumors, MYC is overexpressed by enhanced transcriptional activation, gene amplification, chromosomal rearrangements, or increased protein stabilization. To pharmacologically suppress oncogenic MYC functions, multiple approaches have been applied either to inhibit transcriptional activation of the endogenous MYC gene, or to interfere with biochemical functions of aberrantly activated MYC. Other critical points of attack are targeted protein modification, or destabilization leading to a non-functional MYC oncoprotein. It has been claimed that the natural compound curcumin representing the principal curcumoid of turmeric (Curcuma longa) has anticancer properties although its specificity, efficacy, and the underlying molecular mechanisms have been controversially discussed. Here, we have tested curcumin’s effect on MYC-dependent cell transformation and transcriptional activation, and found that this natural compound interferes with both of these MYC activities. Furthermore, in curcumin-treated cells, the endogenous 60-kDa MYC protein is covalently and specifically cross-linked to one of its transcriptional interaction partners, namely the 434-kDa transformation/transcription domain associated protein (TRRAP). Thereby, endogenous MYC levels are strongly reduced and cells stop to proliferate. TRRAP is a multidomain adaptor protein of the phosphoinositide 3-kinase-related kinases (PIKK) family and represents an important component of many histone acetyltransferase (HAT) complexes. TRRAP is important to mediate transcriptional activation executed by the MYC oncoprotein, but on the other hand TRRAP also negatively regulates protein stability of the tumor suppressor p53 (TP53). Curcumin-mediated covalent binding of MYC to TRRAP reduces the protein amounts of both interaction partners but does not downregulate TP53, so that the growth-arresting effect of wild type TP53 could prevail. Our results elucidate a molecular mechanism of curcumin action that specifically and irreversibly targets two crucial multifunctional cellular players. With regard to their broad impact in cancer, our findings contribute to explain the pleiotropic functions of curcumin, and suggest that this natural spice, or more bioavailable derivatives thereof, may constitute useful adjuvants in the therapy of MYC-dependent and TRRAP-associated human tumors.

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Section: Cell Culture and Cell Transformation Assaymentioning

confidence: 99%

Section: Expression Plasmids Gene Transfer Reporter Gene Assay and Cell Proliferation Analysismentioning

confidence: 99%

Section: Expression Plasmids Gene Transfer Reporter Gene Assay and Cell Proliferation Analysismentioning

confidence: 99%

Section: Curcumin Inhibits Myc-specific Cell Transformationmentioning

confidence: 99%

Section: Curcumin Interferes With Transcriptional Activation Of Mycmentioning

confidence: 99%

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The Diarylheptanoid Curcumin Induces MYC Inhibition and Cross-Links This Oncoprotein to the Coactivator TRRAP

et al. 2021

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BASP1 expression is associated with poor prognosis and is correlated with immune infiltration in gastric cancer

et al. 2023

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BASP1 is a membrane‐bound protein that plays a promotional or inhibitory role in a variety of tumors; however, its role in gastric cancer (GC) and in the immune microenvironment has not been reported. The objectives of this study were to determine whether BASP1 is a valuable prognostic marker for GC and to explore its role in the immune microenvironment of GC. The expression level of BASP1 in GC was analyzed based on the TCGA dataset and further verified using GSE54129 and GSE161533 datasets, immunohistochemistry, and western blotting. The association between BASP1 and clinicopathological characteristics, as well as its predictive value, were examined using the STAD dataset. Cox regression analysis was performed to determine whether BASP1 can be used as an independent prognostic indicator for GC, and a nomogram was constructed to predict OS. The association between BASP1 and immune cell infiltration, immune checkpoints, and immune cell markers was confirmed by enrichment analysis, as well as analysis based on the TIMER and GEPIA databases. BASP1 was observed to be highly expressed in GC and was associated with a poor prognosis. The expression of BASP1 was positively correlated with the expression of immune checkpoints and immune cell markers, as well as immune cell infiltration. Thus, BASP1 may serve as a standalone prognostic indicator for GC. BASP1 is highly correlated with immune processes, and its expression is positively correlated with the degree of immune cell infiltration, immune checkpoints, and immune cell markers.

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Advances in RNA Labeling with Trifluoromethyl Groups

Eichler

Himmelstoß

Plangger

et al. 2023

Chemistry A European J

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Fluorine labeling of ribonucleic acids in conjunction with 19F‐NMR spectroscopy has emerged as a powerful strategy for spectroscopic analysis of RNA structure and dynamics, and RNA– ligand interactions. Here, we present the first syntheses of 2'‐OCF3 guanosine and uridine phosphoramidites, their incorporation into oligoribonucleotides by solid‐phase synthesis and a comprehensive study of their properties. NMR spectroscopic analysis showed that the 2'‐OCF3 modification is associated with preferential C2'‐endo conformation of the U and G ribose in single‐stranded RNA. When paired to the complementary strand, slight destabilization of the duplex caused by the modification was revealed by UV melting curve analysis. Moreover, we demonstrate the power of the 2'‐OCF3 label for NMR spectroscopy by dissecting RNA pseudoknot folding and its binding to a small molecule. Furthermore, the 2'‐OCF3 modification has potential for applications in therapeutic oligonucleotides. To this end, we tested 2'‐OCF3 modified siRNAs in silencing of the BASP1 gene which indicated enhanced performance. Importantly, together with our earlier work, the present study completes the set of 2'‐OCF3 nucleoside phosphoramidites to all four standard nucleobases and hence enables applications that utilize the favorable properties of the 2'‐OCF3 group without any restrictions in placing the modification into the RNA target sequence.

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The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

Cited by 21 publications

References 69 publications

The Diarylheptanoid Curcumin Induces MYC Inhibition and Cross-Links This Oncoprotein to the Coactivator TRRAP

The Diarylheptanoid Curcumin Induces MYC Inhibition and Cross-Links This Oncoprotein to the Coactivator TRRAP

BASP1 expression is associated with poor prognosis and is correlated with immune infiltration in gastric cancer

Advances in RNA Labeling with Trifluoromethyl Groups

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