Disease relevance of NCOA6

• Interactions between activating signal cointegrator-2 and the tumor suppressor retinoblastoma in androgen receptor transactivation [1].
• The NRC gene is also amplified and overexpressed in breast, colon, and lung cancers [2].
• Using this strategy, we have isolated three novel amplified genes (termed AIB1, AIB3, and AIB4) from a cDNA library constructed from the 20q amplified breast cancer cell line BT-474 [3].
• The random phage display peptide D22 and peptides derived from PGC1alpha, SRC1-4, SRC2-3, PRIP/RAP250 and RIP140 yielded the highest TR-FRET signal with RXRbeta LBD in the presence of saturating 9-cis retinoic acid (9-cisRA) [4].
• This binding activity, called TRBP, recognizes the EBV terminal repeats, a locus responsible for interconversion of linear and circular EBV DNA [5].

Psychiatry related information on NCOA6

• We also noticed that NRC/MASC genes appear to be more strongly associated with mental retardation and autism spectrum disorders [6].
• The problem of whether rapid-cycling (RC) bipolar disorder is more frequently associated than non-rapid-cycling (NRC) bipolar disorders with thyroid dysfunction was investigated in two groups of 11 women matched for age and therapy [7].
• METHODS: Review of 40 years of published health studies of the BFD-endemic area of SW Taiwan showed that earlier publications had limited their cancer associations with arsenic levels in artesian well waters and that the reports of Morales et al., NRC, and EPA failed to do so [8].
• Moreover, persons in the NRC group who perceived high levels of racism (vs. no racism or BRC group) during active speech showed larger increases in blood pressure across postspeech rest, anger recall, and subsequent rest (p = .03) [9].

High impact information on NCOA6

• NRC(-/-) mouse embryo fibroblasts spontaneously undergo apoptosis, indicating the importance of NRC as a prosurvival and antiapoptotic gene [2].
• The intrinsic activation potential of NRC is regulated by a C-terminal serine, threonine, leucine-regulatory domain [2].
• Studies with 129S6 NRC(+/-) mice indicate that NRC is a pleiotropic regulator that is involved in growth, development, reproduction, metabolism, and wound healing [2].
• NRC OKs long-delayed survey of human genome diversity [10].
• CONTEXT: In May 1997, the US Nuclear Regulatory Commission (NRC) revised its patient release regulations, allowing for outpatient administration of larger activities of sodium iodide 131I than previously permitted [11].

Chemical compound and disease context of NCOA6

• Vascular endotheliocytes BAE-2 underwent the gradually proceeding cell death until 48 h after reoxygenation (Reox) following 3 h anoxia (Anox), but protected by pre-Anox administration with L-ascorbic acid (Asc)-2-O-phosphate (Asc2P), an autooxidation-resistant Asc derivative, but not by Asc itself [12].
• These data confirm that bipolar disorder, especially during treatment with lithium, is associated with at least subclinical hypothyroidism, and suggest that RC patients do not differ from NRC patients in the prevalence of spontaneous or lithium-induced thyroid hypofunction [7].
• Treatment of massive hemorrhage with liposome encapsulated human hemoglobin (NRC) and hydroxyethyl starch (HES) in beagles [13].
• Anatoxin-a(s) is a guanidine methyl phosphate ester (unprotonated molecular ion equals 252 daltons) isolated from the freshwater cyanobacterium (blue-green alga) Anabaena flos-aquae strain NRC 525-17 [14].
• In this study the current Nuclear Regulatory Commission (NRC) protocol is used to evaluate the stability of Tuskegee cement/cobalt chloride waste form in the presence of Thiobacillus thiooxidans (T. thiooxidans) [15].

Biological context of NCOA6

• Further, the association of TRBP with the DNA-dependent protein kinase (DNA-PK) complex and DNA-independent phosphorylation of TRBP C terminus by DNA-PK point to a potential connection between transcriptional control and chromatin architecture regulation [16].
• These include activating signal cointegrator 2 (ASC-2), a recently isolated transcriptional coactivator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors and numerous other transcription factors [17].
• In this work, we showed that ASC-2 has an indirect, separate binding site for androgen receptor (AR) [1].
• The activation of granulocyte-specific gene expression is increased with the concerted action of another basic regionleucine zipper factor, CCAAT/enhancer-binding protein (C/EBPalpha), and ASC-2, which function in a cooperative manner [18].
• Transient transfection studies further confirmed that the LXXLL-binding affinity correlates with TRBP transcriptional activity [19].

Anatomical context of NCOA6

• A thyroid hormone receptor (TR)-binding protein (TRBP) was cloned by a Sos-Ras yeast two-hybrid system using TRbeta1-ligand binding domain as bait [16].
• NIF-1 was cloned from rat pituitary and human cell lines and was found to interact in vivo and in vitro with NRC [20].
• The identification of dUTPase as a PPAR-interacting protein suggests a possible link between tumorigenic peroxisome proliferators and the enzyme system involved in the maintenance of DNA fidelity [21].
• First, transcriptional activation by CAR was enhanced by cotransfected ASC-2 in CV-1 and HeLa cells [22].
• Functional interaction of transcriptional coactivator ASC-2 and C/EBPalpha in granulocyte differentiation of HL-60 promyelocytic cell [23].

Associations of NCOA6 with chemical compounds

• These results, along with the previous report in which AR was shown to directly interact with Rb (Yeh, S., Miyamoto, H., Nishimura, K., Kang, H., Ludlow, J., Hsiao, P., Wang, C., Su, C., and Chang C. (1998) Biochem. Biophys. Res. Commun. 248, 361-367), suggest that the AR-ASC-2 interactions in vivo may involve Rb [1].
• We isolated a nuclear factor (designated ASC-2) with such properties by using the ligand-binding domain of retinoid X receptor as a bait in a yeast two-hybrid screening [24].
• Activation and interaction of ATF2 with the coactivator ASC-2 are responsive for granulocytic differentiation by retinoic acid [18].
• PIMT (PRIP-interacting protein with methyltransferase domain), an RNA-binding protein with a methyltransferase domain capable of binding S-adenosylmethionine, has been shown previously to interact with nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPAR)-interacting protein) and enhance its coactivator function [25].
• As the differential recruitment of TRBP to ERalpha and ERbeta may rely on S884, our finding provides insight into estrogen signaling and may lead to the development of therapeutic receptor-selective peptide antagonists [19].

Physical interactions of NCOA6

• From these results, we concluded that ASC-2 directly binds to nuclear receptors and recruits CBP to mediate the nuclear receptor transactivation in vivo [26].
• This resulted from the direct protein interaction that the N-terminal transactivation domain of ATF2 interacts with the central region of ASC-2 [18].
• Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase [27].

Regulatory relationships of NCOA6

• The interaction between ATF2 and C/EBPalpha in RA-treated cells was enhanced by the ectopic expression of ASC-2 [18].

Other interactions of NCOA6

• Two distinct nuclear receptor-interaction domains and CREB-binding protein-dependent transactivation function of activating signal cointegrator-2 [26].
• ASC-2 is a recently isolated transcriptional cointegrator molecule, which is amplified in human cancers and stimulates transactivation by nuclear receptors, AP-1, nuclear factor kappaB (NFkappaB), serum response factor (SRF), and numerous other transcription factors [26].
• Furthermore, the receptor transactivation was not enhanced by ASC-2 in the presence of E1A and significantly impaired by overexpressed AD2 [26].
• ATF2-mediated transactivation was also increased by co-transfection of ASC-2 [18].
• Furthermore, analyzing at 20q12-q13 range, we show the existence of three amplification cores, represented by AIB3/AIB4, AIB1, and RMC20C001 [28].

Analytical, diagnostic and therapeutic context of NCOA6

• These three genes were mapped to 20q11 (AIB3 and AIB4) and 20q12 (AIB1) by fluorescence in situ hybridization [3].
• Consistent with an idea that ASC-2 is essential for the nuclear receptor function in vivo, microinjection of anti-ASC-2 antibody abrogated the ligand-dependent transactivation of retinoic acid receptor, and this repression was fully relieved by coinjection of ASC-2-expression vector [24].
• Consistent with these results, chromatin immunoprecipitation experiments revealed that ASC-2 is recruited to the known CAR target genes in a ligand-dependent manner [22].
• DNA fingerprinting: the NRC report [29].
• Using the NRC method and not accounting for the attenuation of photons, the mean dose equivalent to the public exposed to an 131I anti-B1 patient discharged without hospitalization was 4.9 +/- 0.9 mSv (490 +/- 90 mrem) [30].

References