Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA267011 | ENA |
REPOSITORIES: ENA
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Project description: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.
2015-03-12 | GSE63210 | GEO
Project description:Metastasis suppressor 1 (MTSS1) is a 755 amino acid protein found in the cell cytoplasm which binds to actin and promotes cytoskeleton organization and is a known suppressor of lung adenocarcinoma metastasis This study demonstrated that preservation of MTSS1 protein expression in lung adenocarcinoma was associated with a 20% 5-year survival advantage in patients. Furthermore, overexpression of MTSS1 was found to reduce metastasis and disease progression in an in-vivo orthotopic lung adenocarcinoma mouse model. Nuclear factor kappa B (NF-kB), an important nuclear transcription factor, has been shown to be constitutively active in lung adenocarcinoma and strongly associated with the development of metastasis. The NF-kB RelA/p65 subunit is involved in NF-kB heterodimer formation and subsequent nuclear translocation leading to activation of NF-kB responsive gene transcription. Phosphorylation and acetylation of p65 are critical post-translational modifications required for NF-kB activation. In this study, we demonstrate that MTSS1 expression leads to decreased NF-κB mediated gene transcription through inhibition of p65 phosphorylation. These findings uncover a novel mechanism through which MTSS1 may regulate lung adenocarcinoma metastasis by impairment of NF-κB regulated gene transcription.
2024-07-07 | GSE179644 | GEO
Project description:Ribosomal protein S3: a functional component of NF-kB p65 binding complexes
| PRJNA97943 | ENA
Project description:Invasion of bladder cancer (BC) cells from the mucosa into the muscle layer is canonical for BC progression while phospholipase D isoform 1 (PLD1) is known to mediate development of cancer through phosphatidic acid (PA) production. We therefore used in silico, in vitro and in vivo approaches to detail the effect of PLD1 on BC invasion. In BC patients, higher levels of PLD1 expression were associated with poor prognosis. PLD1 knockdown significantly suppressed cellular invasion by human BC cells and matrix metalloproteinase-13 (MMP-13) was observed to be an invasion mediator gene. In our mouse bladder carcinogenesis model, the development of invasive BCs was suppressed by PLD1 knockout and a global transcriptomic analysis in this model indicated MMP-13 as a potential tumor invasion gene with NF-kB (nuclear factor-kB) as its transcription regulator. Furthermore, PA administration increased both MMP-13 expression and NF-kB p65 phosphorylation levels. Collectively, we demonstrate that PLD1 promotes tumor invasion of BC by regulation of MMP-13 expression via phosphorylation of NF-kB p65. Our results suggest that PLD1 is a potential therapeutic target to prevent progression in BC patients.
2022-04-05 | GSE166004 | GEO
Project description:We reported a direct phosphorylation of the Ser547 of the RelA/p65 subunit of NF-kB by ATM kinase. A comparative transcriptomic analyse with HEK293 cells expressing exclusively HA-p65wt or a non-phosphorylable mutant HA-p65S547A was conducted to identify the genes regulated by this phosphorylation after an Etoposide treatment.
2012-05-31 | GSE33990 | GEO
Project description:T cell activation following antigen binding to the T cell receptor (TCR) involves the mobilization of intracellular calcium (Ca2+) to activate the key transcription factors NFAT and NF-κB. The mechanism of NFAT activation by Ca2+ has been determined; however, the role of Ca2+ in controlling NF-κB signaling is poorly understood and the source of Ca2+ required for NF-κB activation is unknown. We demonstrate that TCR- but not TNF- induced NF-κB signaling upstream of IκB kinase (IKK) activation absolutely requires the influx of extracellular Ca2+ via STIM1-dependent CRAC/Orai channels. We further show that Ca2+ influx controls phosphorylation of the NF-κB protein p65 on Ser536 and that this post- translational modification controls its nuclear localization and transcriptional activation. Notably our data reveal that this role for Ca2+ is entirely separate from its upstream control of IκBα degradation, thereby identifying a novel Ca2+- dependent distal step in TCR-induced NF-κB activation. Finally, we demonstrate that this control of distal signaling occurs via Ca2+-dependent PKCk-mediated phosphorylation of p65. Thus, we establish the source of Ca2+ required for TCR induced NF-kB activation and we define a new distal Ca2+-dependent checkpoint in TCR-induced NF-kB signaling that has broad implications for the control of immune cell development and T cell functional specificity. 3 treatments were analyzed, with biological replicates for each treatment. In addition, three timepoints (1 hour, 4 hour, and 8 hour) were examined for each treatment, as well as an untreated control. In total 19 samples were analyzed
2016-01-14 | E-GEOD-76804 | biostudies-arrayexpress
Project description:We reported a direct phosphorylation of the Ser547 of the RelA/p65 subunit of NF-kB by ATM kinase. A comparative transcriptomic analyse with HEK293 cells expressing exclusively HA-p65wt or a non-phosphorylable mutant HA-p65S547A was conducted to identify the genes regulated by this phosphorylation after an Etoposide treatment. HEK293 cells expressing exclusively HA-p65wt or HA-p65S547A were treated during four or eight hours with Etoposide or left untreated. This was performed three times to obtain independent triplicates for the microarray expermiment.
2012-05-30 | E-GEOD-33990 | biostudies-arrayexpress
Project description:NF-kB p65 ChIPseq revealed differential binding of p65 in Treg vs Tconv upon TCR stimulation
2017-09-13 | GSE99319 | GEO
Project description:MTSS1 Suppresses NF-kB Activity in Lung Adenocarcinoma through Repression of RelA/p65 Phosphorylation
| PRJNA744471 | ENA
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO