The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes.

Abstract:

:2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon receptor (AhR) ligands suppress 17beta-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D, and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent degradation of endogenous estrogen receptor alpha (ERalpha). The proteasome inhibitors MG132, PSI, and PSII inhibit the proteasome-dependent effects induced by TCDD, whereas the protease inhibitors EST, calpain inhibitor II, and chloroquine do not affect this response. ERalpha levels in the mouse uterus and breast cancer cells were significantly lower after cotreatment with E plus TCDD than after treatment with E or TCDD alone, and our results indicate that AhR-mediated inhibition of E-induced transactivation is mainly due to limiting levels of ERalpha in cells cotreated with E plus TCDD. TCDD alone or in combination with E increases formation of ubiquitinated forms of ERalpha, and both coimmunoprecipitation and mammalian two-hybrid assays demonstrate that TCDD induces interaction of the AhR with ERalpha in the presence or absence of E. In contrast, E does not induce AhR-ERalpha interactions. Thus, inhibitory AhR-ERalpha cross talk is linked to a novel pathway for degradation of ERalpha in which TCDD initially induces formation of a nuclear AhR complex which coordinately recruits ERalpha and the proteasome complex, resulting in degradation of both receptors.

journal_name

Mol Cell Biol

authors

Wormke M,Stoner M,Saville B,Walker K,Abdelrahim M,Burghardt R,Safe S

doi

10.1128/mcb.23.6.1843-1855.2003

subject

Has Abstract

pub_date

2003-03-01 00:00:00

pages

1843-55

issue

6

eissn

0270-7306

issn

1098-5549

journal_volume

23

pub_type

杂志文章
  • Genetic analysis of cytoprotective functions supported by graded expression of Keap1.

    abstract::Keap1 regulates Nrf2 activity in response to xenobiotic and oxidative stresses. Nrf2 is an essential regulator of cytoprotective genes. Keap1-null mice are lethal by weaning age due to malnutrition caused by severe hyperkeratosis of the upper digestive tract. Analysis of Keap1::Nrf2 double mutant mice revealed that cu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01591-09

    authors: Taguchi K,Maher JM,Suzuki T,Kawatani Y,Motohashi H,Yamamoto M

    更新日期:2010-06-01 00:00:00

  • Monoubiquitination of filamin B regulates vascular endothelial growth factor-mediated trafficking of histone deacetylase 7.

    abstract::Nucleocytoplasmic shuttling of class IIa of histone deacetylases (HDACs) is a key mechanism that controls cell fate and animal development. We have identified the filamin B (FLNB) as a novel HDAC7-interacting protein that is required for temporal and spatial regulation of vascular endothelial growth factor (VEGF)-medi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01146-12

    authors: Su YT,Gao C,Liu Y,Guo S,Wang A,Wang B,Erdjument-Bromage H,Miyagi M,Tempst P,Kao HY

    更新日期:2013-04-01 00:00:00

  • DPH5, a methyltransferase gene required for diphthamide biosynthesis in Saccharomyces cerevisiae.

    abstract::A mutant of Saccharomyces cerevisiae defective in the S-adenosylmethionine (AdoMet)-dependent methyltransferase step of diphthamide biosynthesis was selected by intracellular expression of the F2 fragment of diphtheria toxin (DT) and shown to belong to complementation group DPH5. The DPH5 gene was cloned, sequenced, a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.9.4026

    authors: Mattheakis LC,Shen WH,Collier RJ

    更新日期:1992-09-01 00:00:00

  • Mechanism of B-cell receptor-induced phosphorylation and activation of phospholipase C-gamma2.

    abstract::Phospholipase C-gamma2 (PLC-gamma2) plays an important role in B-cell signaling. Phosphorylation of various tyrosine residues of PLC-gamma2 has been implicated in regulation of its lipase activity. With the use of antibodies specific for each of the putative phosphorylation sites, we have now shown that PLC-gamma2 is ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.22.9986-9999.2004

    authors: Kim YJ,Sekiya F,Poulin B,Bae YS,Rhee SG

    更新日期:2004-11-01 00:00:00

  • Control of the replicative life span of human fibroblasts by p16 and the polycomb protein Bmi-1.

    abstract::The polycomb protein Bmi-1 represses the INK4a locus, which encodes the tumor suppressors p16 and p14(ARF). Here we report that Bmi-1 is downregulated when WI-38 human fibroblasts undergo replicative senescence, but not quiescence, and extends replicative life span when overexpressed. Life span extension by Bmi-1 requ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.1.389-401.2003

    authors: Itahana K,Zou Y,Itahana Y,Martinez JL,Beausejour C,Jacobs JJ,Van Lohuizen M,Band V,Campisi J,Dimri GP

    更新日期:2003-01-01 00:00:00

  • Mouse testes contain two size classes of actin mRNA that are differentially expressed during spermatogenesis.

    abstract::Using several actin isotype-specific cDNA probes, we found actin mRNA of two size classes, 2.1 and 1.5 kilobases (kb), in extracts of polyadenylated and nonpolyadenylated RNA from sexually mature CD-1 mouse testes. Although the 2.1-kb sequence was present in both meiotic and postmeiotic testicular cell types, it decre...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.7.1649

    authors: Waters SH,Distel RJ,Hecht NB

    更新日期:1985-07-01 00:00:00

  • Nonhomologous end joining during restriction enzyme-mediated DNA integration in Saccharomyces cerevisiae.

    abstract::The BamHI restriction enzyme mediates integration of nonhomologous DNA into the Saccharomyces cerevisiae genome (R. H. Schiestl and T. D. Petes, Proc. Natl. Acad. Sci. USA 88:7585-7589, 1991). The present study investigates the mechanism of such events: in particular, the mediating activity of various restriction enzy...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.3.1736

    authors: Manivasakam P,Schiestl RH

    更新日期:1998-03-01 00:00:00

  • mRNA instability in the nucleus due to a novel open reading frame element is a major determinant of the narrow tissue specificity of folate receptor alpha.

    abstract::The folate receptor type alpha (FR-alpha) is a promising tumor marker and target. Here, we investigate the mechanistic basis for the tumor specificity and vast overexpression of FR-alpha. Among representative FR-alpha-positive (HeLa and JAR) and FR-alpha-negative (MG63, Caki1, and HT3) cell lines, the transcription ra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.6.2202-2212.2003

    authors: Zheng X,Kelley K,Elnakat H,Yan W,Dorn T,Ratnam M

    更新日期:2003-03-01 00:00:00

  • The K-fgf/hst oncogene induces transformation through an autocrine mechanism that requires extracellular stimulation of the mitogenic pathway.

    abstract::The K-fgf/hst oncogene encodes a secreted growth factor of the fibroblast growth factor (FGF) family. The ability of K-fgf-transformed cells to grow in soft agar and in serum-free medium is inhibited by anti-K-FGF neutralizing antibodies, consistent with an autocrine mechanism of transformation. The transformed proper...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.2.1138

    authors: Talarico D,Basilico C

    更新日期:1991-02-01 00:00:00

  • Essential role of STAT3 in body weight and glucose homeostasis.

    abstract::STAT3 is a ubiquitous transcription factor that is indispensable during early embryogenesis. To study the functions of STAT3 postnatally, we generated conditional STAT3-deficient mice. To that end, STAT3(lox/lox) mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.1.258-269.2004

    authors: Cui Y,Huang L,Elefteriou F,Yang G,Shelton JM,Giles JE,Oz OK,Pourbahrami T,Lu CY,Richardson JA,Karsenty G,Li C

    更新日期:2004-01-01 00:00:00

  • Alternative splicing of a human alpha-tropomyosin muscle-specific exon: identification of determining sequences.

    abstract::The human alpha-tropomyosin gene hTMnm has two mutually exclusive versions of exon 5 (NM and SK), one of which is expressed specifically in skeletal muscle (exon SK). A minigene construct expresses only the nonmuscle (NM) isoform when transfected into COS-1 cells and both forms when transfected into myoblasts. Twenty-...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.9.3872

    authors: Graham IR,Hamshere M,Eperon IC

    更新日期:1992-09-01 00:00:00

  • Differential regulation of human interferon A gene expression by interferon regulatory factors 3 and 7.

    abstract::Differential expression of the human interferon A (IFN-A) gene cluster is modulated following paramyxovirus infection by the relative amounts of active interferon regulatory factor 3 (IRF-3) and IRF-7. IRF-3 expression activates predominantly IFN-A1 and IFN-B, while IRF-7 expression induces multiple IFN-A genes. IFN-A...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01805-08

    authors: Génin P,Lin R,Hiscott J,Civas A

    更新日期:2009-06-01 00:00:00

  • Overexpression of the cochaperone CHIP enhances Hsp70-dependent folding activity in mammalian cells.

    abstract::CHIP is a cochaperone of Hsp70 that inhibits Hsp70-dependent refolding in vitro. However, the effect of altered expression of CHIP on the fate of unfolded proteins in mammalian cells has not been determined. Surprisingly, we found that overexpression of CHIP in fibroblasts increased the refolding of proteins after the...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.14.4948-4958.2003

    authors: Kampinga HH,Kanon B,Salomons FA,Kabakov AE,Patterson C

    更新日期:2003-07-01 00:00:00

  • Inheritance of extrachromosomal rDNA in Physarum polycephalum.

    abstract::In the acellular slime mold Physarum polycephalum, the several hundred genes coding for rRNA are located on linear extrachromosomal DNA molecules of a discrete size, 60 kilobases. Each molecule contains two genes that are arranged in a palindromic fashion and separated by a central spacer region. We investigated how r...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.4.635

    authors: Ferris PJ,Vogt VM,Truitt CL

    更新日期:1983-04-01 00:00:00

  • Sperm-specific expression of angiotensin-converting enzyme (ACE) is mediated by a 91-base-pair promoter containing a CRE-like element.

    abstract::The gene encoding the testis isozyme of angiotensin-converting enzyme (testis ACE) is one example of the many genes expressed uniquely during spermatogenesis. This protein is expressed by developing germ cells late in their development and results from the activation of a sperm-specific promoter that is located within...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.1.18

    authors: Howard T,Balogh R,Overbeek P,Bernstein KE

    更新日期:1993-01-01 00:00:00

  • Mitotic arrest caused by the amino terminus of Xenopus cyclin B2.

    abstract::Progression through mitosis requires the inactivation of the protein kinase activity of the p34cdc2-cyclin complex by a mechanism involving the degradation of cyclin. We have examined the stability in Xenopus egg extracts of radiolabeled Xenopus or sea urchin B-type cyclins synthesized in reticulocyte lysates. Xenopus...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.3.1480

    authors: van der Velden HM,Lohka MJ

    更新日期:1993-03-01 00:00:00

  • Differential and inefficient splicing of a broadly expressed Drosophila erect wing transcript results in tissue-specific enrichment of the vital EWG protein isoform.

    abstract::In this report, we document an unusual mode of tissue-enriched gene expression that is primarily mediated by alternative and inefficient splicing. We have analyzed posttranscriptional regulation of the Drosophila erect wing gene, which provides a vital neuronal function and is essential for the formation of certain mu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.6.3998

    authors: Koushika SP,Soller M,DeSimone SM,Daub DM,White K

    更新日期:1999-06-01 00:00:00

  • Protein kinase C-theta isoenzyme selective stimulation of the transcription factor complex AP-1 in T lymphocytes.

    abstract::T-lymphocyte stimulation requires activation of several protein kinases, including the major phorbol ester receptor protein kinase C (PKC), ultimately leading to induction of lymphokines, such as interleukin-2 (IL-2). The revelant PKC isoforms which are involved in the activation cascades of nuclear transcription fact...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.4.1842

    authors: Baier-Bitterlich G,Uberall F,Bauer B,Fresser F,Wachter H,Grunicke H,Utermann G,Altman A,Baier G

    更新日期:1996-04-01 00:00:00

  • The ARID family transcription factor bright is required for both hematopoietic stem cell and B lineage development.

    abstract::Bright/Arid3a has been characterized both as an activator of immunoglobulin heavy-chain transcription and as a proto-oncogene. Although Bright expression is highly B lineage stage restricted in adult mice, its expression in the earliest identifiable hematopoietic stem cell (HSC) population suggests that Bright might h...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01448-10

    authors: Webb CF,Bryant J,Popowski M,Allred L,Kim D,Harriss J,Schmidt C,Miner CA,Rose K,Cheng HL,Griffin C,Tucker PW

    更新日期:2011-03-01 00:00:00

  • The Pu.1 locus is differentially regulated at the level of chromatin structure and noncoding transcription by alternate mechanisms at distinct developmental stages of hematopoiesis.

    abstract::The Ets family transcription factor PU.1 is crucial for the regulation of hematopoietic development. Pu.1 is activated in hematopoietic stem cells and is expressed in mast cells, B cells, granulocytes, and macrophages but is switched off in T cells. Many of the transcription factors regulating Pu.1 have been identifie...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00905-07

    authors: Hoogenkamp M,Krysinska H,Ingram R,Huang G,Barlow R,Clarke D,Ebralidze A,Zhang P,Tagoh H,Cockerill PN,Tenen DG,Bonifer C

    更新日期:2007-11-01 00:00:00

  • Mapping of a replication origin within the promoter region of two unlinked, abundantly transcribed actin genes of Physarum polycephalum.

    abstract::We analyzed the replication of two unlinked actin genes, ardB and ardC , which are abundantly transcribed in the naturally synchronous plasmodium of the slime mold Physarum polycephalum. Detection and size measurements of single-stranded nascent replication intermediates (RIs) demonstrate that these two genes are conc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.3.968

    authors: Bénard M,Lagnel C,Pallotta D,Pierron G

    更新日期:1996-03-01 00:00:00

  • Genetic tagging of tumor cells with retrovirus vectors: clonal analysis of tumor growth and metastasis in vivo.

    abstract::Retrovirus vector infection was used to introduce large numbers of unique genetic markers into tumor cell populations for the purpose of analyzing comparative changes in the clonal composition of metastatic versus that of nonmetastatic tumors during their progressive growth in vivo. The cell lines used were SP1, a non...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.8.3143

    authors: Korczak B,Robson IB,Lamarche C,Bernstein A,Kerbel RS

    更新日期:1988-08-01 00:00:00

  • Exchange protein activated by cyclic AMP (Epac)-mediated induction of suppressor of cytokine signaling 3 (SOCS-3) in vascular endothelial cells.

    abstract::Here, we demonstrate that elevation of intracellular cyclic AMP (cAMP) in vascular endothelial cells (ECs) by either a direct activator of adenylyl cyclase or endogenous cAMP-mobilizing G protein-coupled receptors inhibited the tyrosine phosphorylation of STAT proteins by an interleukin 6 (IL-6) receptor trans-signali...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00207-06

    authors: Sands WA,Woolson HD,Milne GR,Rutherford C,Palmer TM

    更新日期:2006-09-01 00:00:00

  • Concerted action of the transcriptional activators REB1, RAP1, and GCR1 in the high-level expression of the glycolytic gene TPI.

    abstract::In Saccharomyces cerevisiae, the TPI gene product, triosephosphate isomerase, makes up about 2% of the soluble cellular protein. Using in vitro and in vivo footprinting techniques, we have identified four binding sites for three factors in the 5' noncoding region of TPI: a REB1-binding site located at positions -401 t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.1.543

    authors: Scott EW,Baker HV

    更新日期:1993-01-01 00:00:00

  • axl, a transforming gene isolated from primary human myeloid leukemia cells, encodes a novel receptor tyrosine kinase.

    abstract::Using a sensitive transfection-tumorigenicity assay, we have isolated a novel transforming gene from the DNA of two patients with chronic myelogenous leukemia. Sequence analysis indicates that the product of this gene, axl, is a receptor tyrosine kinase. Overexpression of axl cDNA in NIH 3T3 cells induces neoplastic t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.10.5016

    authors: O'Bryan JP,Frye RA,Cogswell PC,Neubauer A,Kitch B,Prokop C,Espinosa R 3rd,Le Beau MM,Earp HS,Liu ET

    更新日期:1991-10-01 00:00:00

  • Receptor clustering is involved in Reelin signaling.

    abstract::The Reelin signaling cascade plays a crucial role in the correct positioning of neurons during embryonic brain development. Reelin binding to apolipoprotein E receptor 2 (ApoER2) and very-low-density-lipoprotein receptor (VLDLR) leads to phosphorylation of disabled 1 (Dab1), an adaptor protein which associates with th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.24.3.1378-1386.2004

    authors: Strasser V,Fasching D,Hauser C,Mayer H,Bock HH,Hiesberger T,Herz J,Weeber EJ,Sweatt JD,Pramatarova A,Howell B,Schneider WJ,Nimpf J

    更新日期:2004-02-01 00:00:00

  • Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons.

    abstract::Understanding the mechanisms that drive the differentiation of dopaminergic (DA) neurons is crucial for successful development of novel therapies for Parkinson's disease, in which DA neurons progressively degenerate. However, the mechanisms underlying the differentiation-promoting effects of Wnt5a on DA precursors are...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00745-12

    authors: Čajánek L,Ganji RS,Henriques-Oliveira C,Theofilopoulos S,Koník P,Bryja V,Arenas E

    更新日期:2013-01-01 00:00:00

  • Interdependent interactions between TFIIB, TATA binding protein, and DNA.

    abstract::Temperature-sensitive mutants of TFIIB that are defective for essential interactions were isolated. One mutation (G204D) results in disruption of a protein-protein contact between TFIIB and TATA binding protein (TBP), while the other (K272I) disrupts an interaction between TFIIB and DNA. The TBP gene was mutagenized, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.24.8735-8743.2002

    authors: Buratowski RM,Downs J,Buratowski S

    更新日期:2002-12-01 00:00:00

  • The amino-terminal region of Drosophila MSL1 contains basic, glycine-rich, and leucine zipper-like motifs that promote X chromosome binding, self-association, and MSL2 binding, respectively.

    abstract::In Drosophila melanogaster, X chromosome dosage compensation is achieved by doubling the transcription of most X-linked genes. The male-specific lethal (MSL) complex is required for this process and binds to hundreds of sites on the male X chromosome. The MSL1 protein is essential for X chromosome binding and serves a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.20.8913-8924.2005

    authors: Li F,Parry DA,Scott MJ

    更新日期:2005-10-01 00:00:00

  • Sequence elements essential for function of the Xenopus laevis ribosomal DNA enhancers.

    abstract::The intergenic spacer region of the Xenopus laevis ribosomal DNA contains multiple elements which are either 60 or 81 base pairs long. Clusters of these elements have previously been shown to act as position- and distance-independent enhancers on an RNA polymerase I promoter when located in cis. By a combination of de...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.10.4282

    authors: Pikaard CS,Reeder RH

    更新日期:1988-10-01 00:00:00