Disease relevance of Ncor2

• Here, we show that IKK is activated in colorectal tumors concomitant with the presence of phosphorylated SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) corepressor that is aberrantly localized in the cytoplasm [1].
• The AR mutation T877A (Thr877-->Ala), which is frequently found in prostate cancer and affects the ligand-induced conformational change of the AR, considerably reduced the repressive action of N-CoR [2].

High impact information on Ncor2

• Here, we report that transcriptional activation mediated by liganded nuclear receptors unexpectedly requires the actions of two highly related F box/WD-40-containing factors, TBL1 and TBLR1, initially identified as components of an N-CoR corepressor complex [3].
• N-CoR controls differentiation of neural stem cells into astrocytes [4].
• Recruitment of protein phosphatase-1 to a specific binding site on N-CoR exerts a reciprocal effect on the cellular localization of N-CoR [4].
• Association of PPRE-bound PV with corepressors [e.g., nuclear receptor corepressor (NCoR)] that led to transcriptional repression was independent of T3 and troglitazone [5].
• Deletion of an AML1-ETO C-terminal NcoR/SMRT-interacting region strongly induces leukemia development [6].

Biological context of Ncor2

• Unexpectedly, N-CoR and a specific deacetylase were also required for transcriptional activation of one class of retinoic acid response element [7].
• These data redefine a structurally and functionally more related nuclear receptor corepressor family and suggest an additional role for SMRTe in the regulation of cycle-specific gene expression in diverse signaling pathways [8].
• We find that SMRTe expression is regulated during cell cycle progression and SMRTe transcripts are present in many embryonic tissues [8].
• The nuclear receptor corepressors NCoR and SMRT decrease peroxisome proliferator-activated receptor gamma transcriptional activity and repress 3T3-L1 adipogenesis [9].
• Functional interactions between specific receptors and N-CoR or SMRT corepressor complexes are regulated, positively or negatively, by diverse signal transduction pathways [10].

Anatomical context of Ncor2

• In mammalian two-hybrid assays with two different cell lines and in cell-free pull-down and whole-cell immunoprecipitation assays, the corepressors NCoR (nuclear receptor corepressor) and SMRT (silencing mediator of retinoid and thyroid hormone receptor) associate with agonist and antagonist complexes of GRs [11].
• While dissociation of NCoR and SMRT results in derepression of the ABCA1 gene in macrophages, it is not sufficient for derepression of the SREBP1c gene [12].
• First, Northern blotting revealed TRH and NCoR mRNA expressions to be inversely correlated during postnatal development and as a function of thyroid status [13].
• Third, over-expression of full length NCoR and SMRT in the hypothalamus abolished T(3)-dependent repression of TRH-luciferase [13].
• Second, in situ hybridization showed that NCoR and SMRT mRNA expression profiles in the paraventricular nucleus were distinct from that of TRH mRNA [13].

Associations of Ncor2 with chemical compounds

• Such corepressors include the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoid and thyroid hormone receptors (SMRT) [9].
• The nuclear receptor corepressor (NCoR) and the related factor known as silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) are essential components of multiprotein complexes that mediate active repression by unliganded nuclear receptors [14].
• Glutathione S-transferase pulldown assays confirmed a direct interaction between HNF4alpha1 and receptor interaction domain 2 of SMRT [15].
• This isoleucine is also conserved in N2 but not in the corresponding S2 domain in SMRT [16].
• Small amounts of co-transfected N-CoR repressed CPA (cyproterone acetate)- and mifepristone (RU486)-mediated AR activity, but did not affect agonist (R1881)-induced AR activity [2].
• Stimulation of estradiol-induced ERalpha activity by SMRT overexpression occurred in HeLa and MCF-7 cells, but not HepG2 cells, indicating that these positive effects are cell type specific [17].

Regulatory relationships of Ncor2

• Overexpression of the corepressor silencing mediator for retinoic acid and thyroid hormone receptors (SMRT) suppressed AP-1 activity [18].

Analytical, diagnostic and therapeutic context of Ncor2

• The relative expression levels of both fluorescent proteins are estimated, and YFP-NCoR subnuclear organization is quantified based on the mean focal body size and relative intensity [19].
• Chromatin immunoprecipitation assay further demonstrated that, despite the presence of ligands, NCoR was recruited to PPRE-bound PV on a PPARgamma-target gene, the lipoprotein lipase, in vivo, suggesting the dominant action of PV on PPARgamma-mediated transcriptional activity [5].

References