Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gene expression profiling of altered NF-kB p65 ser536 phosphorylation in prostate cancer cells

ABSTRACT: Aberrant regulation of NF-kB pathway is believed to be a major event contributing to malignant transformation and progression of prostate cancer (PCa). P65 consists of a DNA-binding and dimerization domain (RHD), nuclear localization signal (NLS) and transactivation domains (TA1 and TA2). The c-terminal 30 amino acids (TA1 domain) comprise the most important transactivation domain and NF-kB transactivation may be regulated by multiple phosphorylation in this domain. This p536 is located in TA1 domain and is conserved in human, mouse, chicken. We previously discovered that p536 is present in majority of PCa and associated with ERG expression indicating that ERG can significantly enhance phosphorylation of p65 at Ser536 in vivo. We have successfully generated a dominant negative (DN) p65 which has been mutated (S536A) such that it cannot be phosphorylated at Ser 536 and cannot carry out Ser536 phosphorylation dependent functions. We also generated two mutants S536D and S536E which are the phosphomimetic mutant that resembles phospho-p65 and can be detected by anti-phospho-p65 antibody. We carried out microarray studies and discovered a set of p536 regulated genes compared with wild type p65 regulated gene set.

ORGANISM(S): Homo sapiens

PROVIDER: GSE63210 | GEO | 2015/03/12

SECONDARY ACCESSION(S): PRJNA267011

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Inhibiting Androgen Receptor Splice Variants with Cysteine-Selective Irreversible Covalent Inhibitors to Treat Prostate Cancer

Project description:Prostate cancer (PCa) affects over 250,000 men in the US. Androgen Receptor (AR) signaling inhibitors are the mainstay therapeutics for PCa. Advanced PCa that expresses AR splice variants (AR-SVs) does not respond to current therapeutic strategies. In this manuscript, we uncovered the physicochemical properties of the intrinsically-disordered transactivation domain of AR and AR-SV and developed novel AR irreversible covalent antagonists (SARICA) to the transactivation domain for the treatment of advanced PCa. SARICAs were also used to identify a potential binding region in the AR and AR-SV transactivation domain.

2022-12-31 | GSE215335 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics

Project description:NFkB RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (ChIPseq) and functional (RNAseq in knockouts) datasets. We then dissected each gene's regulatory strategy by testing RelA variants in a novel primary-cell genetic complementation assay. All endogenous target genes required that RelA makes DNA-base-specific contacts, and none could be activated by the DNA binding domain alone. However, endogenous target genes differed widely in how they employ the two transactivation domains. Through model-aided analysis of the dynamic timecourse data we reveal gene-specific synergy and redundancy of TA1 and TA2. Given that post-translational modifications control TA1 activity and intrinsic affinity for coactivators determines TA2 activity, the differential TA logics suggests context-dependent vs. context-independent control of endogenous RelA-target genes. While some inflammatory initiators appear to require co-stimulatory TA1 activation, inflammatory resolvers are a part of the NFkB RelA core response.

2020-01-30 | GSE132863 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics (ChIP-seq.WT.MEFs)

2020-01-30 | GSE132792 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics [ChIP-seq RNAPII]

Project description:NFkB RelA is the potent transcriptional activator of inflammatory response genes. We stringently defined a list of direct RelA target genes by integrating physical (ChIPseq) and functional (RNAseq in knockouts) datasets. We then dissected each gene’s regulatory strategy by testing RelA variants in a novel primary-cell genetic complementation assay. All endogenous target genes required that RelA makes DNA-base-specific contacts, and none could be activated by the DNA binding domain alone. However, endogenous target genes differed widely in how they employ the two transactivation domains. Through model-aided analysis of the dynamic timecourse data we reveal gene-specific synergy and redundancy of TA1 and TA2. Given that post-translational modifications control TA1 activity and intrinsic affinity for coactivators determines TA2 activity, the differential TA logics suggests context-dependent vs. context-independent control of endogenous RelA-target genes. While some inflammatory initiators appear to require co-stimulatory TA1 activation, inflammatory resolvers are a part of the NFkB RelA core response.

2020-01-30 | GSE140967 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics [MEFs_2]

2020-01-30 | GSE132654 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics [caRNAseq]

2020-01-30 | GSE132602 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics (RNA-seq.WT.p53ko.MEFs_4)

2020-01-30 | GSE132791 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics [MEFs_3]

2020-01-30 | GSE132774 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics [BMDM]

2020-01-30 | GSE132539 | GEO

Dissecting the regulatory strategies of NFkB RelA target genes in the inflammatory response reveals differential transactivation logics [MEF]