Targeting MYC Transcription with Small Peptide Derived from KSHV Transactivator (CUT&RUN)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA726881 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14402210_1.fastq.gz | Fastqsanger.gz | |||
| SRR14402210_2.fastq.gz | Fastqsanger.gz | |||
| SRR14402211_1.fastq.gz | Fastqsanger.gz | |||
| SRR14402211_2.fastq.gz | Fastqsanger.gz | |||
| SRR14402212_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:Targeting MYC Transcription with Small Peptide Derived from KSHV Transactivator
| PRJNA726876 | ENA
Project description:Herpesviruses rely on host cell transcription and translation machineries for replication. Viral proteins thus function to redirect multiple cellular proteins for viral replication. In herpesvirus replicating cells, host cell gene transcription is frequently down-regulated because important transcriptional apparatuses are appropriated by viral transcription factors. Here we show that an evolutionally-shaped viral protein sequence is a great starting material for unique drug development to modulate cellular transcription. Cellular c-Myc protein (MYC) is overexpressed in over 70% of all types of cancer cells and therefore a very attractive target to control cancer cell growth. We identified a small functional peptide derived from the Kaposi's sarcoma-associated herpesvirus transactivator (K-Rta), which strongly attenuates MYC expression, reduces cell proliferation, and selectively kills cancer cells in both tissue culture and a xenograft tumor mouse model. Mechanistically, the peptide blocks promoter-enhancer interactions by preventing coactivator complex consisting of Nuclear receptor coactivator 2, p300, and SWI/SNF proteins from engaging the MYC promoter in leukemia cells. Target gene profiling with SLAM-seq suggests that the viral peptide attenuates MYC expression through a mechanism likely different from that of BET bromodomain inhibitors. Furthermore, fusing the 13 amino acids peptide with humanized anti-CD22 single chain armed the antibody drug with cell killing ability, and inhibited cell growth in soft agar. Our studies thus demonstrate the utility of the peptide sequence as a therapeutics module, which may be used to modulate MYC activity in a cell type-specific manner.
2021-12-01 | GSE173724 | GEO
Project description:Targeting MYC Transcription with Small Peptide Derived from KSHV Transactivator (RNA-Seq)
| PRJNA727986 | ENA
Project description:Targeting MYC Transcription with Small Peptide Derived from KSHV Transactivator (SLAM-Seq)
| PRJNA728449 | ENA
Project description:Herpesviruses rely on host cell transcription and translation machineries for replication. Viral proteins thus function to redirect multiple cellular proteins for viral replication. In herpesvirus replicating cells, host cell gene transcription is frequently down-regulated because important transcriptional apparatuses are appropriated by viral transcription factors. Here we show that an evolutionally-shaped viral protein sequence is a great starting material for unique drug development to modulate cellular transcription. Cellular c-Myc protein (MYC) is overexpressed in over 70% of all types of cancer cells and therefore a very attractive target to control cancer cell growth. We identified a small functional peptide derived from the Kaposi's sarcoma-associated herpesvirus transactivator (K-Rta), which strongly attenuates MYC expression, reduces cell proliferation, and selectively kills cancer cells in both tissue culture and a xenograft tumor mouse model. Mechanistically, the peptide blocks promoter-enhancer interactions by preventing coactivator complex consisting of Nuclear receptor coactivator 2, p300, and SWI/SNF proteins from engaging the MYC promoter in leukemia cells. Target gene profiling with SLAM-seq suggests that the viral peptide attenuates MYC expression through a mechanism likely different from that of BET bromodomain inhibitors. Furthermore, fusing the 13 amino acids peptide with humanized anti-CD22 single chain armed the antibody drug with cell killing ability, and inhibited cell growth in soft agar. Our studies thus demonstrate the utility of the peptide sequence as a therapeutics module, which may be used to modulate MYC activity in a cell type-specific manner.
2021-12-01 | GSE174115 | GEO
Project description:Herpesviruses rely on host cell transcription and translation machineries for replication. Viral proteins thus function to redirect multiple cellular proteins for viral replication. In herpesvirus replicating cells, host cell gene transcription is frequently down-regulated because important transcriptional apparatuses are appropriated by viral transcription factors. Here we show that an evolutionally-shaped viral protein sequence is a great starting material for unique drug development to modulate cellular transcription. Cellular c-Myc protein (MYC) is overexpressed in over 70% of all types of cancer cells and therefore a very attractive target to control cancer cell growth. We identified a small functional peptide derived from the Kaposi's sarcoma-associated herpesvirus transactivator (K-Rta), which strongly attenuates MYC expression, reduces cell proliferation, and selectively kills cancer cells in both tissue culture and a xenograft tumor mouse model. Mechanistically, the peptide blocks promoter-enhancer interactions by preventing coactivator complex consisting of Nuclear receptor coactivator 2, p300, and SWI/SNF proteins from engaging the MYC promoter in leukemia cells. Target gene profiling with SLAM-seq suggests that the viral peptide attenuates MYC expression through a mechanism likely different from that of BET bromodomain inhibitors. Furthermore, fusing the 13 amino acids peptide with humanized anti-CD22 single chain armed the antibody drug with cell killing ability, and inhibited cell growth in soft agar. Our studies thus demonstrate the utility of the peptide sequence as a therapeutics module, which may be used to modulate MYC activity in a cell type-specific manner.
2021-12-01 | GSE174031 | GEO
Project description:Targeting MYC Transcription with Small Peptide Derived from KSHV Transactivator (RNA-Seq analysis of PDX tumors)
| PRJNA727988 | ENA
Project description:Herpesviruses rely on host cell transcription and translation machineries for replication. Viral proteins thus function to redirect multiple cellular proteins for viral replication. In herpesvirus replicating cells, host cell gene transcription is frequently down-regulated because important transcriptional apparatuses are appropriated by viral transcription factors. Here we show that an evolutionally-shaped viral protein sequence is a great starting material for unique drug development to modulate cellular transcription. Cellular c-Myc protein (MYC) is overexpressed in over 70% of all types of cancer cells and therefore a very attractive target to control cancer cell growth. We identified a small functional peptide derived from the Kaposi's sarcoma-associated herpesvirus transactivator (K-Rta), which strongly attenuates MYC expression, reduces cell proliferation, and selectively kills cancer cells in both tissue culture and a xenograft tumor mouse model. Mechanistically, the peptide blocks promoter-enhancer interactions by preventing coactivator complex consisting of Nuclear receptor coactivator 2, p300, and SWI/SNF proteins from engaging the MYC promoter in leukemia cells. Target gene profiling with SLAM-seq suggests that the viral peptide attenuates MYC expression through a mechanism likely different from that of BET bromodomain inhibitors. Furthermore, fusing the 13 amino acids peptide with humanized anti-CD22 single chain armed the antibody drug with cell killing ability, and inhibited cell growth in soft agar. Our studies thus demonstrate the utility of the peptide sequence as a therapeutics module, which may be used to modulate MYC activity in a cell type-specific manner.
2021-12-01 | GSE174033 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-12-01 | GSE173725 | GEO
Project description:Kaposi's sarcoma (KS), is an AIDS-associated neoplasm caused by the KS herpesvirus (KSHV). A mouse model of KSHV-dependent tumorigenicity, allowed us to induce KSHV viral-episome loss following tumor development to test the plausibility of “hit and run” mechanism by KSHV. RNA-seq-transcriptome analysis and CpG-methylation were performed on KSHV positive cells, KSHV positive tumors and tumors that developed following viral-episome loss. During KSHV tumorigenesis, hypo-methylation was detected of oncogenic and differentiation pathways. In contrast, during tumorigenesis following KSHV-episome loss, a tendency towards hyper-methylation was detected. We found the same set of innate-immunity related mutations undetected in KSHV-infected cells but present in all KSHV-positive tumors, indicating that pre-existing host mutations that provide an in vivo growth advantage are clonally-selected and contribute to KSHV-tumorigenesis. We found de novo mutations related to cell proliferation that, together with the PDGFRAD842V, were responsible for driving tumorigenesis in absence of the KSHV-episomes. Virally-induced irreversible genetic and epigenetic oncogenic alteration supports the possibility of “hit and run” KSHV-sarcomagenesis consistent with the existence of LANA-negative spindle-cells in KS lesions.
2020-01-23 | GSE144101 | GEO