Publications
196 results found
Morganstein DL, Parker MG, 2007, Role of nuclear receptor coregulators in metabolism., Expert Rev Endocrinol Metab, Vol: 2, Pages: 797-807
Understanding the molecular regulation of metabolism will lead to a better understanding of the pathogenesis and treatment of common metabolic conditions, including obesity and diabetes. Nuclear receptors are a family of transcription factors, many of which play major roles in regulating metabolic genes in key tissues. They function by recruiting coregulators to the promoters of metabolic genes that can either activate or repress transcription. This review examines the roles of these coregulators in the control of metabolism in adipose tissue and skeletal muscle, and discusses how they result in coordinated and regulated control of metabolic pathways. In particular, the ligand-dependent recruitment of both coactivators and corepressors has potential implications for the treatment of obesity and diabetes.
Kiskinis E, Hallberg M, Christian M, et al., 2007, RIP140 directs histone and DNA methylation to silence <i>Ucp1</i> expression in white adipocytes, EMBO JOURNAL, Vol: 26, Pages: 4831-4840, ISSN: 0261-4189
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- Citations: 82
Herzog B, Hallberg M, Seth A, et al., 2007, The nuclear receptor cofactor, receptor-interacting protein 140, is required for the regulation of hepatic lipid and glucose metabolism by liver X receptor, MOLECULAR ENDOCRINOLOGY, Vol: 21, Pages: 2687-2697, ISSN: 0888-8809
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- Citations: 74
Seth A, Steel JH, Nichol D, et al., 2007, The transcriptional corepressor RIP140 regulates oxidative metabolism in skeletal muscle, Cell Metabolism, Vol: 6, Pages: 236-245, ISSN: 1932-7420
Nuclear receptor signaling plays an important role in energy metabolism. In this study we demonstrate that the nuclear receptor corepressor RIP140 is a key regulator of metabolism in skeletal muscle. RIP140 is expressed in a fiber type-specific manner, and manipulation of its levels in null, heterozygous, and transgenic mice demonstrate that low levels promote while increased expression suppresses the formation of oxidative fibers. Expression profiling reveals global changes in the expression of genes implicated in both myofiber phenotype and metabolic functions. Genes involved in fattyacid oxidation, oxidative phosphorylation, and mitochondrial biogenesis are upregulated in the absence of RIP140. Analysis of cultured myofibers demonstrates that the changes in expression are intrinsic to muscle cells and that nuclear receptor-regulated genes are direct targets for repression by RIP140. Therefore RIP140 is an important signaling factor in the regulation of skeletal muscle function and physiology.
Debevec D, Christian M, Morganstein D, et al., 2007, Receptor interacting protein 140 regulates expression of uncoupling protein 1 in adipocytes through specific peroxisome proliferator activated receptor isoforms and estrogen-related receptor alpha, Molecular Endocrinology, Vol: 21, Pages: 1581-1592
van Mil SWC, Milona A, Dixon PH, et al., 2007, Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy., Gastroenterology, Vol: 133, Pages: 507-516
Dahlman-Wright K, Cavailles V, Fuqua SA, et al., 2006, International Union of Pharmacology.: LXIV.: Estrogen receptors, PHARMACOLOGICAL REVIEWS, Vol: 58, Pages: 773-781, ISSN: 0031-6997
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- Citations: 420
Parker MG, Christian M, White R, 2006, The nuclear receptor co-repressor RIP140 controls the expression of metabolic gene networks, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 34, Pages: 1103-1106, ISSN: 0300-5127
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- Citations: 20
Lopez-Garcia J, Periyasamy M, Thomas RS, et al., 2006, ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases, Nucleic Acids Research, Vol: 34, Pages: 6126-6136, ISSN: 1362-4962
The regulation of gene expression by estrogen receptor-α (ERα) requires the coordinated and temporal recruitment of diverse sets of transcriptional co-regulator complexes, which mediate nucleosome remodelling and histone modification. Using ERα as bait in a yeast two-hybrid screen, we have identified a novel ERα-interacting protein, ZNF366, which is a potent corepressor of ERα activity. The interaction between ZNF366 and ERα has been confirmed in vitro and in vivo, and is mediated by the zinc finger domains of the two proteins. Further, we show that ZNF366 acts as a corepressor by interacting with other known ERα corepressors, namely RIP140 and CtBP, to inhibit expression of estrogen-responsive genes in vivo. Together, our results indicate that ZNF366 may play an important role in regulating the expression of genes in response to estrogen.
Huq MDM, Gupta P, Tsai N-P, et al., 2006, Suppression of receptor interacting protein 140 repressive activity by protein arginine methylation, EMBO JOURNAL, Vol: 25, Pages: 5094-5104, ISSN: 0261-4189
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- Citations: 79
Nichol D, Christian M, Steel JH, et al., 2006, RIP140 expression is stimulated by estrogen-related receptor alpha during adipogenesis, Journal of Biological Chemistry, Vol: 281, Pages: 32140-32147, ISSN: 1083-351X
RIP140 is a corepressor for nuclear receptors that regulates energy expenditure in adipose tissue by suppressing the expression of clusters of metabolic genes involved in glucose and lipid metabolism. The gene encoding RIP140/Nrip1 contains only one coding exon but has multiple promoters and 5′ non-coding exons that are subject to alternative splicing. In adipocytes we have defined a promoter, referred to as P2, that is preferentially utilized and activated during adipogenesis. Expression studies and chromatin immunoprecipitation experiments indicate that estrogen-related receptor α (ERRα), the level of which increases during adipogenesis in parallel with RIP140, stimulates transcription from the P2 promoter. Further analysis indicates that ERRα is capable of activating RIP140 gene transcription by two mechanisms, directly by binding to an estrogen receptor element/ERR element at –650/–633 and indirectly through Sp1 binding sites in the proximal promoter. Thus, the up-regulation of RIP140 by ERRα during adipogenesis may provide an inhibitory feedback mechanism to control the expression of many nuclear receptor target genes.
Garcia-Pedrero JM, Kiskinis E, Parker MG, et al., 2006, The SWI/SNF chromatin remodeling subunit BAF57 is a critical regulator of estrogen receptor function in breast cancer cells, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 281, Pages: 22656-22664
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- Citations: 76
Christian M, White R, Parker MG, 2006, Metabolic regulation by the nuclear receptor corepressor RIP140, TRENDS IN ENDOCRINOLOGY AND METABOLISM, Vol: 17, Pages: 243-250, ISSN: 1043-2760
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- Citations: 92
Kiskinis E, Garcia-Pedrero JM, Villaronga MA, et al., 2006, Identification of BAF57 mutations in human breast cancer cell lines, BREAST CANCER RESEARCH AND TREATMENT, Vol: 98, Pages: 191-198, ISSN: 0167-6806
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- Citations: 22
Brosens JJ, Lam EWF, Parker MG, 2006, Inflammation and sex steroid receptors: A motif for change, CELL, Vol: 124, Pages: 466-468, ISSN: 0092-8674
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- Citations: 4
Powelka AM, Seth A, Virbasius JV, et al., 2006, Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes, JOURNAL OF CLINICAL INVESTIGATION, Vol: 116, Pages: 125-136, ISSN: 0021-9738
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- Citations: 184
Belandia B, Parker MG, 2006, Nuclear receptor regulation gears up another Notch., Nucl Recept Signal, Vol: 4
In this perspective we describe examples of crosstalk between nuclear receptors (NRs) and Notch signaling by means of direct functional interactions between components of both pathways. This crosstalk may provide eukaryotic organisms with molecular mechanisms for the coordination of llong-distance endocrine signals with cell-to-cell juxtacrine communication.
Christian M, Kiskinis E, Debevec D, et al., 2005, RIP140-targeted repression of gene expression in adipocytes, MOLECULAR AND CELLULAR BIOLOGY, Vol: 25, Pages: 9383-9391, ISSN: 0270-7306
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- Citations: 146
Tullet JMA, Pocock V, Steel JH, et al., 2005, Multiple signaling defects in the absence of RIP140 impair both cumulus expansion and follicle rupture, ENDOCRINOLOGY, Vol: 146, Pages: 4127-4137, ISSN: 0013-7227
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- Citations: 33
Steel JH, White R, Parker MG, 2005, Role of the RIP140 corepressor in ovulation and adipose biology, Journal of Endocrinology, Vol: 185, Pages: 1-9, ISSN: 1479-6805
RIP140 is a ligand-dependent corepressor for most, if not all, nuclear receptors. It is expressed widely in many different tissues, but the phenotype of mice devoid of RIP140 indicates that it plays a crucial role in the ovary and in adipose biology. Ovarian expression of RIP140 is cell-type-specific during follicular development and it is essential for oocyte release during ovulation, but not for luteinization of mature ovarian follicles. In adipose tissue, RIP140 is essential for normal fat accumulation and RIP140-null mice show decreased lipid storage even on a high-fat diet, with upregulation of mitochondrial uncoupling protein (UCP1) in some fat depots. Thus RIP140 plays a crucial role in female fertility and in energy homeostasis, and could be a target for infertility treatment, new contraceptive strategies or prevention of obesity.
Belandia B, Powell SM, García-Pedrero JM, et al., 2005, Hey1, a mediator of notch signaling, is an androgen receptor corepressor, MOLECULAR AND CELLULAR BIOLOGY, Vol: 25, Pages: 1425-1436, ISSN: 0270-7306
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- Citations: 110
Lucey MJ, Chen DS, Lopez-Garcia J, et al., 2005, T:G mismatch-specific thymine-DNA glycosylase (TDG) as a coregulator of transcription interacts with SRC1 family members through a novel tyrosine repeat motif, NUCLEIC ACIDS RESEARCH, Vol: 33, Pages: 6393-6404, ISSN: 0305-1048
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- Citations: 36
Parker M, White R, Leonardsson G, et al., 2004, Identification of RIP140 as a nuclear receptor cofactor with a role in female reproduction, Ernst Schering Research Foundation workshop, Pages: 23-31, ISSN: 0947-6075
Leonardsson G, Steel JH, Christian M, et al., 2004, Nuclear receptor corepressor RIP140 regulates fat accumulation, Proceedings of the National Academy of Sciences of the United States of America, Vol: 101, Pages: 8437-8442, ISSN: 0027-8424
Christian M, Tullet JM, Parker MG, 2004, Characterization of four autonomous repression domains in the corepressor receptor interacting protein 140., J Biol Chem, Vol: 279(15), Pages: 15645-15651
Receptor interacting protein (RIP) 140 is a corepressor that can be recruited to nuclear receptors by means of LXXLL motifs. We have characterized four distinct autonomous repression domains in RIP140, termed RD1-4, that are highly conserved in mammals and birds. RD1 at the N terminus represses transcription in the presence of trichostatin A, suggesting that it functions by a histone deacetylase (HDAC)-independent mechanism. The repressive activity of RD2 is dependent upon carboxyl-terminal binding protein recruitment to two specific binding sites. Use of specific inhibitors indicates that RD2, RD3, and RD4 are capable of functioning by HDAC-dependent and HDAC-independent mechanisms, depending upon cell type.
Landles C, Chalk S, Steel JH, et al., 2003, The thyroid hormone receptor-associated protein TRAP220 is required at distinct embryonic stages in placental, cardiac, and hepatic development, MOLECULAR ENDOCRINOLOGY, Vol: 17, Pages: 2418-2435, ISSN: 0888-8809
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- Citations: 49
Belandia B, Parker MG, 2003, Nuclear receptors: A rendezvous for chromatin remodeling factors, CELL, Vol: 114, Pages: 277-280, ISSN: 0092-8674
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- Citations: 94
Parker M, Leonardsson G, White R, et al., 2003, Identification of RIP140 as a nuclear receptor cofactor with a role in female reproduction, FEBS LETTERS, Vol: 546, Pages: 149-153, ISSN: 0014-5793
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- Citations: 12
Brosens JJ, Parker MG, 2003, Gene expression: Oestrogen receptor hijacked, NATURE, Vol: 423, Pages: 487-488, ISSN: 0028-0836
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- Citations: 18
Ciana P, Raviscioni M, Mussi P, et al., 2003, <i>In vivo</i> imaging of transcriptionally active estrogen receptors, NATURE MEDICINE, Vol: 9, Pages: 82-86, ISSN: 1078-8956
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- Citations: 239
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