ING2 (inhibitor of growth family, member 2)

Review on ING2 (inhibitor of growth family, member 2), with data on DNA, on the protein encoded, and where the gene is implicated

Characterization of the SIDDHARTA-2 luminosity monitor

A luminosity monitor, based on plastic scintillator detectors, has been developed for the SIDDHARTA-2 experiment aiming to perform high precision measurements of kaonic atoms and was installed in 2020 on the DAFNE $e^+e^-$ collider at LNF (Laboratori Nazionali di Frascati, INFN). The main goal of this system is to provide the~instantaneous and integrated luminosity of the DAFNE facility by measuring the rate of $K^+K^-$ correlated pairs emitted by the phi meson decay. This task requires an accurate timing of the DAQ signals, as well as timing resolution below 1ns, in order to disentangle the $K^\pm$ signals from the background minimum ionizing particles (MIPs) produced during the $e^+e^-$ collisions at DAFNE. In this paper the luminosity monitor concept as well as its laboratory characterization and the first results inside DAFNE are presented.Comment: Published in JINS

Spectroscopy of kaonic atoms at DAFNE and J-PARC

The interaction of antikaons (K^{-}) with nucleons and nuclei in the low-energy regime represents a very active research field in hadron physics. A unique and rather direct experimental access to the antikaon-nucleon scattering lengths is provided by precision X-ray spectroscopy of transitions in low-lying states in the lightest kaonic atoms (i.e. kaonic hydrogen and deuterium). In the SIDDHARTA experiment at the electron-positron collider DAFNE of LNFINFN we measured the most precise values of the strong interaction observables in conic hydrogen. The strong interaction on the 1s ground state of the electromagnetically bound K-p atom causes an energy shift and broadening of the 1s state. SIDDHARTA will extend the spectroscopy to kaonic deuterium to get access to the antikaon-neutron interaction and thus the isospin dependent scattering lengths. At J-PARC a kaon beam is used in a complementary experiment with a different setup for spectroscopy of kaonic deuterium atoms. The talk will give an overview of the of the upcoming experiments SIDDHARTA and the complementary experiment at J-PARC.Furthermore, the implications of the experiments for the theory of low-energy strong interaction with strangeness will be discussed

Nuclear receptor corepressors

The ability of NR LBDs to transfer repression function to a heterologous DNA binding domain, and the cross-squelching of repression by untethered LBDs, has suggested that repression is mediated by interactions with putative cellular corepressor proteins. The yeast-two hybrid screen for protein interactors has proven to be the key to the isolation and characterization of corepressors. This short review will focus on N-CoR and SMRT

Analysis of Thyroid Response Element Activity during Retinal Development

Thyroid hormone (TH) signaling components are expressed during retinal development in dynamic spatial and temporal patterns. To probe the competence of retinal cells to mount a transcriptional response to TH, reporters that included thyroid response elements (TREs) were introduced into developing retinal tissue. The TREs were placed upstream of a minimal TATA-box and two reporter genes, green fluorescent protein (GFP) and human placental alkaline phosphatase (PLAP). Six of the seven tested TREs were first tested in vitro where they were shown to drive TH-dependent expression. However, when introduced into the developing retina, the TREs reported in different cell types in both a TH-dependent and TH-independent manner, as well as revealed specific spatial patterns in their expression. The role of the known thyroid receptors (TR), TRα and TRβ, was probed using shRNAs, which were co-electroporated into the retina with the TREs. Some TREs were positively activated by TR+TH in the developing outer nuclear layer (ONL), where photoreceptors reside, as well as in the outer neuroblastic layer (ONBL) where cycling progenitor cells are located. Other TREs were actively repressed by TR+TH in cells of the ONBL. These data demonstrate that non-TRs can activate some TREs in a spatially regulated manner, whereas other TREs respond only to the known TRs, which also read out activity in a spatially regulated manner. The transcriptional response to even simple TREs provides a starting point for understanding the regulation of genes by TH, and highlights the complexity of transcriptional regulation within developing tissue

Interactions of SKIP/NCoA-62, TFIIB, and retinoid X receptor with vitamin D receptor helix H10 residues

The vitamin D receptor (VDR) is a ligand-dependent transcription factor that heterodimerizes with retinoid X receptor (RXR) and interacts with the basal transcription machinery and transcriptional cofactors to regulate target gene activity. The p160 coactivator GRIP1 and the distinct coregulator Ski-interacting protein (SKIP)/NCoA-62 synergistically enhance ligand-dependent VDR transcriptional activity. Both coregulators bind directly to and form a ternary complex with VDR, with GRIP1 contacting the activation function-2 (AF-2) domain and SKIP/NCoA-62 interacting through an AF-2 independent interface. It was previously reported that SKIP/NCoA-62 interaction with VDR was independent of the heterodimerization interface (specifically, helices H10/H11). In contrast, the present study defines specific residues within a conserved and surface-exposed region of VDR helix H10 that are required for interaction with SKIP/NCoA-62 and for full ligand-dependent transactivation activity. SKIP/NCoA-62, the basal transcription factor TFIIB, and RXR all interacted with VDR helix H10 mutants at reduced levels compared with wild type in the absence of ligand and exhibited different degrees of increased interaction upon ligand addition. Thus, SKIP/NCoA-62 interacts with VDR at a highly conserved region not previously associated with coregulator binding to regulate transactivation by a molecular mechanism distinct from that of p160 coactivators

kaonic atoms experiment at the daφne collider by siddharta siddharta 2

The excellent quality kaon beam provided by the DA\PhiΦNE collider of LNF-INFN (Italy) together with SIDDHARTA/SIDDHARTA-2 new experimental techniques, as very precise and fast-response X-ray detectors, allow to perform unprecedented measurements on light kaonic atoms crucial for a deeper understanding of the low-energy quantum chromodynamics (QCD) in the strangeness sector. In this paper an overview of the main results obtained by the SIDDHARTA collaboration, as well as the future plans related to the SIDDHARTA-2 experiment, are discussed

probing strong interaction with siddharta 2

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Choline Kinase Alpha as an Androgen Receptor Chaperone and Prostate Cancer Therapeutic Target.

BACKGROUND: The androgen receptor (AR) is a major drug target in prostate cancer (PCa). We profiled the AR-regulated kinome to identify clinically relevant and druggable effectors of AR signaling. METHODS: Using genome-wide approaches, we interrogated all AR regulated kinases. Among these, choline kinase alpha (CHKA) expression was evaluated in benign (n = 195), prostatic intraepithelial neoplasia (PIN) (n = 153) and prostate cancer (PCa) lesions (n = 359). We interrogated how CHKA regulates AR signaling using biochemical assays and investigated androgen regulation of CHKA expression in men with PCa, both untreated (n = 20) and treated with an androgen biosynthesis inhibitor degarelix (n = 27). We studied the effect of CHKA inhibition on the PCa transcriptome using RNA sequencing and tested the effect of CHKA inhibition on cell growth, clonogenic survival and invasion. Tumor xenografts (n = 6 per group) were generated in mice using genetically engineered prostate cancer cells with inducible CHKA knockdown. Data were analyzed with χ(2) tests, Cox regression analysis, and Kaplan-Meier methods. All statistical tests were two-sided. RESULTS: CHKA expression was shown to be androgen regulated in cell lines, xenografts, and human tissue (log fold change from 6.75 to 6.59, P = .002) and was positively associated with tumor stage. CHKA binds directly to the ligand-binding domain (LBD) of AR, enhancing its stability. As such, CHKA is the first kinase identified as an AR chaperone. Inhibition of CHKA repressed the AR transcriptional program including pathways enriched for regulation of protein folding, decreased AR protein levels, and inhibited the growth of PCa cell lines, human PCa explants, and tumor xenografts. CONCLUSIONS: CHKA can act as an AR chaperone, providing, to our knowledge, the first evidence for kinases as molecular chaperones, making CHKA both a marker of tumor progression and a potential therapeutic target for PCa.This work was supported by a Cancer Research UK program grant (to DEN) and also by the US Department of Defense (Prostate Cancer Research Program Transformative Impact Award, grant ID W81XWH-13-2-0093; WDT and SMD), PCFA/Cancer Australia/Movember (grant IDs 1012337 and 1043482; WDT and LAS), Cancer Australia (grant ID 1043497; WDT and JC) and The Ray and Shirl Norman Cancer Research Trust (WDT and LAS). The Dame Roma Mitchell Cancer Research Laboratories were supported by an establishment grant from the PCFA (ID 2011/0452). FO was supported by a PhD project grant from Prostate Cancer UK (S10-10). LAS is supported by a Young Investigator Award from the Prostate Cancer Foundation (the Foundation 14 award)