Abstract:
:The cytochrome P450 (CYP) gene products such as CYP3A and CYP2B are essential for the metabolism of steroid hormones and xenochemicals including prescription drugs. Nuclear receptor SXR/PXR (steroid and xenobiotic receptor/pregnenolone X receptor) has been shown both biochemically and genetically to activate CYP3A genes, while similar studies have established constitutive androstane receptor (CAR) as a CYP2B regulator. The response elements in these genes are also distinct, furthering the concept of independent regulation. Unexpectedly, we found that SXR can regulate CYP2B, both in cultured cells and in transgenic mice via adaptive recognition of the phenobarbital response element (PBRE). In a type of functional symmetry, orphan receptor CAR was also found to activate CYP3A through previously defined SXR/PXR response elements. These observations not only provide a rational explanation for the activation of multiple CYP gene classes by certain xenobiotics, but also reveal the existence of a metabolic safety net that confers a second layer of protection to the harmful effects of toxic compounds and at the same time increases the propensity for drug-drug interactions.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Xie W,Barwick JL,Simon CM,Pierce AM,Safe S,Blumberg B,Guzelian PS,Evans RMdoi
10.1101/gad.846800subject
Has Abstractpub_date
2000-12-01 00:00:00pages
3014-23issue
23eissn
0890-9369issn
1549-5477journal_volume
14pub_type
杂志文章abstract::Programmed cell death occurs in a highly reproducible manner during Caenorhabditis elegans development. We demonstrate that, during embryogenesis, miR-35 and miR-58 bantam family microRNAs (miRNAs) cooperate to prevent the precocious death of mothers of cells programmed to die by repressing the gene egl-1, which encod...
journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
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更新日期:1996-12-01 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2006-12-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章,评审
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更新日期:2015-02-01 00:00:00
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journal_title:Genes & development
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abstract::The chromo domain was identified as a homologous protein motif between Polycomb (Pc)--a member of the Pc-group genes encoding transcriptional repressors of the homeotic genes--and HP1--a heterochromatin-associated protein encoded by the suppressor of position effect variegation gene Su(var)205. Together with previous ...
journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:1998-05-15 00:00:00
abstract::Regulated cell expansion is an important determinant of organ shape in higher plants. The sabre mutation results in abnormal cell expansion in Arabidopsis. There is a shift in the orientation of expansion evident primarily in root cortex cells. The SABRE gene has been cloned and found to encode a novel protein. Reduct...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.3.330
更新日期:1995-02-01 00:00:00
abstract::Epigenetic modifications of chromatin play an important role in the regulation of gene expression. KMT4/Dot1 is a conserved histone methyltransferase capable of methylating chromatin on Lys79 of histone H3 (H3K79). Here we report the identification of a multisubunit Dot1 complex (DotCom), which includes several of the...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1898410
更新日期:2010-03-15 00:00:00
abstract::The Swi/Snf chromatin remodeling complex functions to alter nucleosome positions by either sliding nucleosomes on DNA or the eviction of histones. The presence of histone acetylation and activator-dependent recruitment and retention of Swi/Snf is important for its efficient function. It is not understood, however, why...
journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
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journal_title:Genes & development
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journal_title:Genes & development
pub_type: 杂志文章,评审
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2006-06-15 00:00:00
abstract::Treatment of early Xenopus embryos with retinoic acid (RA) produces a concentration-dependent series of defects in anterior axial structures that range from small deletions to embryos lacking heads. The graded series of axial defects obtained after RA administration to early embryos appears to result, in part, from ac...
journal_title:Genes & development
pub_type: 杂志文章
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journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.8.1023
更新日期:1997-04-15 00:00:00
abstract::Innate immunity against pathogen infection is an evolutionarily conserved process among multicellular organisms. Arabidopsis SNC1 encodes a Resistance protein that combines attributes of multiple mammalian pattern recognition receptors. Utilizing snc1 as an autoimmune model, we identified a discrete protein complex co...
journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2007-06-15 00:00:00
abstract::Transgenic mice expressing wild-type murine p53 under the control of the mouse mammary tumor virus long terminal repeat (MMTV LTR) undergo progressive renal failure due to abnormal kidney development. Similar phenotypes are observed in two transgenic lines that express wild-type p53 within the ureteric bud but not in ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.7.836
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journal_title:Genes & development
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journal_title:Genes & development
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更新日期:2008-07-15 00:00:00
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journal_title:Genes & development
pub_type: 杂志文章
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更新日期:2011-04-01 00:00:00