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Ncoa6  -  nuclear receptor coactivator 6

Mus musculus

Synonyms: AIB3, ASC-2, ASC2, Activating signal cointegrator 2, Aib3, ...
 
 
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Disease relevance of Ncoa6

  • To examine whether AIB3 reduction affects mammary tumorigenesis, we generated wild-type mouse mammary tumor virus/polyoma middle-T (WT/PyMT) and AIB3(+/-)/PyMT mice [1].
  • Microcystins from Anabaena flos-aquae NRC 525-17 [2].
  • Tumor metastasis and invasion were shown to be inhibited by the 2-O-phosphorylated form (Asc2P) of L-ascorbic acid (Asc); intact Asc did not inhibit tumor invasion when added once, but appreciably inhibited it upon repeated addition [3].
  • Relative to controls, who received NRC recommended levels of these nutrients, all diets with marginal essential trace elements impacted development, as demonstrated by effects on birth weight (CaMg, Fe) or weaning weight (Fe, Zn, P) [4].
 

High impact information on Ncoa6

  • Furthermore, relative to the wild type, ASC-2+/- mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/- islets [5].
  • Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic beta-cells [5].
  • In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells [5].
  • Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/- mice [5].
  • The NRC/MASC is a rich source of genetic variation and provides a platform for understanding relationships of disease phenotype amenable to systematic studies such as the Genes to Cognition research consortium (www.genes2cognition.org) that links human and mouse genetics with proteomic studies [6].
 

Chemical compound and disease context of Ncoa6

 

Biological context of Ncoa6

 

Anatomical context of Ncoa6

  • Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR [9].
  • Here, we demonstrate that AIB3 protein is mainly located in the nuclei of mammary epithelial cells and tumor cells and its levels are elevated in mammary epithelial cells at middle pregnant stage and in mammary tumor cells [1].
  • During pregnancy, PRIP-deficient mammary glands exhibited decreased alveolar density [11].
  • Interestingly, Northern blot and in situ hybridization analyses reveal that RAP250 is widely expressed with the highest expression in reproductive organs (testis, prostate and ovary) and brain [12].
  • The lactating PRIP-deficient glands contained scant lobuloalveoli with many adipocytes, whereas the wild type glands were composed of virtually no adipocytes but mostly lobuloalveoli [11].
 

Associations of Ncoa6 with chemical compounds

  • The ductal branching of mammary glands in response to estrogen treatment was attenuated in PRIP mutant glands [11].
  • These results also indicate that the biological function of AIB3 is not redundant with other classes of nuclear receptor coactivators such as PBP and members of the steroid receptor coactivator family [13].
  • A major functional subcomponent of the synaptic machinery is a multiprotein complex of glutamate receptors and adhesion proteins with associated adaptor and signalling enzymes totally 185 proteins known as the N-methyl-d-aspartate receptor complex/MAGUK associated signalling complex (NRC/MASC) [6].
  • As a consequence, PRIP-deficiency in liver did not protect from acetaminophen-induced hepatic necrosis, unlike that exerted by PBP deficiency [14].
  • Young C57BL/6 mice receiving the 100% NRC (30% ethanol) or the 60% NRC (30% ethanol) diets for 7 weeks presented alterations in the T and B cell phenotype comparable with the alterations observed in mice receiving the Lieber-DeCarli diet for 19 weeks [15].
 

Regulatory relationships of Ncoa6

 

Other interactions of Ncoa6

 

Analytical, diagnostic and therapeutic context of Ncoa6

References

  1. Haploid inactivation of the amplified-in-breast cancer 3 coactivator reduces the inhibitory effect of peroxisome proliferator-activated receptor gamma and retinoid X receptor on cell proliferation and accelerates polyoma middle-T antigen-induced mammary tumorigenesis in mice. Zhang, H., Kuang, S.Q., Liao, L., Zhou, S., Xu, J. Cancer Res. (2004) [Pubmed]
  2. Microcystins from Anabaena flos-aquae NRC 525-17. Harada, K., Ogawa, K., Kimura, Y., Murata, H., Suzuki, M., Thorn, P.M., Evans, W.R., Carmichael, W.W. Chem. Res. Toxicol. (1991) [Pubmed]
  3. Tumor invasion is inhibited by phosphorylated ascorbate via enrichment of intracellular vitamin C and decreasing of oxidative stress. Nagao, N., Nakayama, T., Etoh, T., Saiki, I., Miwa, N. J. Cancer Res. Clin. Oncol. (2000) [Pubmed]
  4. Developmental aluminum toxicity in mice can be modulated by low concentrations of minerals (Fe, Zn, P, Ca, Mg) in the diet. Golub, M.S., Germann, S.L., Keen, C.L. Biological trace element research. (2003) [Pubmed]
  5. Regulation of insulin secretion and beta-cell mass by activating signal cointegrator 2. Yeom, S.Y., Kim, G.H., Kim, C.H., Jung, H.D., Kim, S.Y., Park, J.Y., Pak, Y.K., Rhee, D.K., Kuang, S.Q., Xu, J., Han, D.J., Song, D.K., Lee, J.W., Lee, K.U., Kim, S.W. Mol. Cell. Biol. (2006) [Pubmed]
  6. Synapse proteomics of multiprotein complexes: en route from genes to nervous system diseases. Grant, S.G., Marshall, M.C., Page, K.L., Cumiskey, M.A., Armstrong, J.D. Hum. Mol. Genet. (2005) [Pubmed]
  7. The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flos-aquae NRC 525-17. Mahmood, N.A., Carmichael, W.W. Toxicon (1986) [Pubmed]
  8. Coactivator PRIP, the peroxisome proliferator-activated receptor-interacting protein, is a modulator of placental, cardiac, hepatic, and embryonic development. Zhu, Y.J., Crawford, S.E., Stellmach, V., Dwivedi, R.S., Rao, M.S., Gonzalez, F.J., Qi, C., Reddy, J.K. J. Biol. Chem. (2003) [Pubmed]
  9. Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR. Zhu, Y., Kan, L., Qi, C., Kanwar, Y.S., Yeldandi, A.V., Rao, M.S., Reddy, J.K. J. Biol. Chem. (2000) [Pubmed]
  10. The nuclear hormone receptor coactivator NRC is a pleiotropic modulator affecting growth, development, apoptosis, reproduction, and wound repair. Mahajan, M.A., Das, S., Zhu, H., Tomic-Canic, M., Samuels, H.H. Mol. Cell. Biol. (2004) [Pubmed]
  11. Null mutation of peroxisome proliferator-activated receptor-interacting protein in mammary glands causes defective mammopoiesis. Qi, C., Kashireddy, P., Zhu, Y.T., Rao, S.M., Zhu, Y.J. J. Biol. Chem. (2004) [Pubmed]
  12. Cloning and characterization of RAP250, a novel nuclear receptor coactivator. Caira, F., Antonson, P., Pelto-Huikko, M., Treuter, E., Gustafsson, J.A. J. Biol. Chem. (2000) [Pubmed]
  13. Deletion of the cancer-amplified coactivator AIB3 results in defective placentation and embryonic lethality. Kuang, S.Q., Liao, L., Zhang, H., Pereira, F.A., Yuan, Y., DeMayo, F.J., Ko, L., Xu, J. J. Biol. Chem. (2002) [Pubmed]
  14. Peroxisome proliferator-activated receptor (PPAR)-binding protein (PBP) but not PPAR-interacting protein (PRIP) is required for nuclear translocation of constitutive androstane receptor in mouse liver. Guo, D., Sarkar, J., Ahmed, M.R., Viswakarma, N., Jia, Y., Yu, S., Sambasiva Rao, M., Reddy, J.K. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  15. Alterations in mouse Peyer's patch lymphocyte phenotype after ethanol consumption. Lopez, M.C., Watzl, B., Colombo, L.L., Watson, R.R. Alcohol (1997) [Pubmed]
  16. Transcriptional coactivator PRIP, the peroxisome proliferator-activated receptor gamma (PPARgamma)-interacting protein, is required for PPARgamma-mediated adipogenesis. Qi, C., Surapureddi, S., Zhu, Y.J., Yu, S., Kashireddy, P., Rao, M.S., Reddy, J.K. J. Biol. Chem. (2003) [Pubmed]
  17. The human RAP250 gene: genomic structure and promoter analysis. Antonson, P., Al-Beidh, F., Matthews, J., Gustafsson, J.A. Gene (2004) [Pubmed]
  18. PRIP promotes tumor formation through enhancing serum-responsive factor-mediated FOS expression. Zhu, Y.T., Hu, L., Qi, C., Zhu, Y.J. J. Biol. Chem. (2009) [Pubmed]
  19. Spatial distribution of the messenger ribonucleic acid and protein of the nuclear receptor coactivator, amplified in breast cancer-3, in mice. Zhang, H., Liao, L., Kuang, S.Q., Xu, J. Endocrinology (2003) [Pubmed]
 
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