ArticleMolecular and cellular biology2007
Tissue- and nuclear receptor-specific function of the C-terminal LXXLL motif of coactivator NCoA6/AIB3 in mice.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
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- Identification of Neuritin 1 as a local metabolic regulator of brown adipose tissue.Nature communications · 2025Article
- Diagnostic yield and novel candidate genes by next generation sequencing in 166 children with intrahepatic cholestasis.Hepatology international · 2024Article
- Interactions between leucines within the signal peptides of megalin and stanniocalcin-1 are crucial for regulation of mitochondrial metabolism.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Knockout of SRC-1 and SRC-3 in Mice Decreases Cardiomyocyte Proliferation and Causes a Noncompaction Cardiomyopathy Phenotype.International journal of biological sciences · 2015Article
- Stage-dependent and locus-specific role of histone demethylase Jumonji D3 (JMJD3) in the embryonic stages of lung development.PLoS genetics · 2014Article
- Nuclear receptors and epigenetic regulation: opportunities for nutritional targeting and disease prevention.Advances in nutrition (Bethesda, Md.) · 2014Review
- Transient replication of Hepatitis C Virus sub-genomic RNA in murine cell lines is enabled by miR-122 and varies with cell passage.PloS one · 2014Article
- NCOA6 differentially regulates the expression of the CYP2C9 and CYP3A4 genes.Pharmacological research · 2011Article
- Identification and characterization of the alternatively spliced nuclear receptor coactivator-6 isoforms.International journal of biological sciences · 2011Article
- Four enzymes cooperate to displace histone H1 during the first minute of hormonal gene activation.Genes & development · 2011Article
- The cooperative function of nuclear receptor coactivator 1 (NCOA1) and NCOA3 in placental development and embryo survival.Molecular endocrinology (Baltimore, Md.) · 2010Article
- PPARgamma1 and LXRalpha face a new regulator of macrophage cholesterol homeostasis and inflammatory responsiveness, AEBP1.Nuclear receptor signaling · 2010Review
- Key roles for MED1 LxxLL motifs in pubertal mammary gland development and luminal-cell differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Coactivators in PPAR-Regulated Gene Expression.PPAR research · 2010Article
- Characterization of ASC-2 as an antiatherogenic transcriptional coactivator of liver X receptors in macrophages.Molecular endocrinology (Baltimore, Md.) · 2009Article
- A tumor suppressive coactivator complex of p53 containing ASC-2 and histone H3-lysine-4 methyltransferase MLL3 or its paralogue MLL4.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Identification of Flightless-I as a substrate of the cytokine-independent survival kinase CISK.The Journal of biological chemistry · 2009Article
- Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Roles of histone H3-lysine 4 methyltransferase complexes in NR-mediated gene transcription.Progress in molecular biology and translational science · 2009Review
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3 authors at 1 institution in 1 country.
Funding
Abstract
Although the LXXLL motif of nuclear receptor (NR) coactivators is essential for interaction with NRs, its role has not been assessed in unbiased animal models. The nuclear receptor coactivator 6 (NCoA6; also AIB3, PRIP, ASC-2, TRBP, RAP250, or NRC) is a coactivator containing an N-terminal LXXLL-1 (L1) and a C-terminal L2. L1 interacts with many NRs, while L2 interacts with the liver X receptor alpha (LXRalpha) and the estrogen receptor alpha (ERalpha). We generated mice in which L2 was mutated into AXXAL (L2m) to disrupt its interaction with LXRalpha and ERalpha. NCoA6(L2m/L2m) mice exhibited normal reproduction, mammary gland morphogenesis, and ERalpha target gene expression. In contrast, when treated with an LXRalpha agonist, lipogenesis and the LXRalpha target gene expression were significantly reduced in NCoA6(L2m/L2m) mice. The induction of Cyp7A1 expression by a high-cholesterol diet was impaired in NCoA6(L2m/L2m) mice, which reduced bile acid synthesis in the liver and excretion in the feces and resulted in cholesterol accumulation in the liver and blood. These results demonstrate that L2 plays a tissue- and NR-specific role: it is required for NCoA6 to mediate LXRalpha-regulated lipogenesis and cholesterol/bile acid homeostasis in the liver but not required for ERalpha function in the mammary gland.
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