Loss of JunB activity enhances stromelysin 1 expression in a model of the epithelial-to-mesenchymal transition of mouse skin tumors.

Abstract:

:Chemical carcinogenesis in mouse skin has been useful in delineating the molecular events that underlie squamous cell carcinoma progression. A late event in this progression, the epithelial-to-mesenchymal transition (EMT), is characterized by the loss of epithelial markers and the presence of mesenchymal markers. One mesenchymal marker associated with this transition is the matrix metalloproteinase stromelysin 1 (Str-1). To examine the molecular mechanisms regulating the expression of Str-1 during the EMT, genetically related mouse skin tumor cell lines representing the epithelial (B9(SQ)) and mesenchymal (A5(SP)) phenotypes were studied. As expected, B9(SQ) cells did not make Str-1, while A5(SP) cells did. B9(SQ)-A5(SP) somatic hybrids did not make Str-1, suggesting that a critical regulatory factor was a B9(SQ)-specific repressor. Str-1 promoter analysis revealed that a canonical AP-1 site was sufficient to maintain differential reporter gene activity. This result correlated with the observed loss of binding of the transcriptionally inactive JunB-Fra-2 AP-1 complex from B9(SQ) cells, being replaced primarily by the more active JunD-Fra-2 complex in A5(SP) cells. The higher level of JunB binding to both DNA and Fra-2 correlated with its hyperphosphorylation by Jun N-terminal kinase, an activity that was significantly higher in B9(SQ) cells. In the somatic hybrids, JunB gene expression was highly upregulated, a condition that also was sufficient to repress the expression of the endogenous Str-1 gene in A5(SP) cells. These data suggested that alterations in JunB activity, by changes in either phosphorylation or gene expression, contributed to the phenotypic differences that occur in this model of the EMT.

journal_name

Mol Cell Biol

authors

Hulboy DL,Matrisian LM,Crawford HC

doi

10.1128/MCB.21.16.5478-5487.2001

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

5478-87

issue

16

eissn

0270-7306

issn

1098-5549

journal_volume

21

pub_type

杂志文章
  • The absence of Ser389 phosphorylation in p53 affects the basal gene expression level of many p53-dependent genes and alters the biphasic response to UV exposure in mouse embryonic fibroblasts.

    abstract::Phosphorylation is important in p53-mediated DNA damage responses. After UV irradiation, p53 is phosphorylated specifically at murine residue Ser389. Phosphorylation mutant p53.S389A cells and mice show reduced apoptosis and compromised tumor suppression after UV irradiation. We investigated the underlying cellular pr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01610-07

    authors: Bruins W,Bruning O,Jonker MJ,Zwart E,van der Hoeven TV,Pennings JL,Rauwerda H,de Vries A,Breit TM

    更新日期:2008-03-01 00:00:00

  • Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR.

    abstract::Previously we demonstrated that the heat shock transcription factor Hsf1 is indispensable for transformation of mammary epithelial cells by the Her2 oncogene. Since Hsf1 affects oncogene-induced senescence (OIS), these findings suggest that Hsf1 affects tumor initiation when OIS plays a role. Indeed, here we report th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.05921-11

    authors: Gabai VL,Meng L,Kim G,Mills TA,Benjamin IJ,Sherman MY

    更新日期:2012-03-01 00:00:00

  • Role for Nhp6, Gcn5, and the Swi/Snf complex in stimulating formation of the TATA-binding protein-TFIIA-DNA complex.

    abstract::The TATA-binding protein (TBP), TFIIA, and TFIIB interact with promoter DNA to form a complex required for transcriptional initiation, and many transcriptional regulators function by either stimulating or inhibiting formation of this complex. We have recently identified TBP mutants that are viable in wild-type cells b...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.24.18.8312-8321.2004

    authors: Biswas D,Imbalzano AN,Eriksson P,Yu Y,Stillman DJ

    更新日期:2004-09-01 00:00:00

  • Two distinct mechanisms of transcriptional control operate on c-myc during differentiation of HL60 cells.

    abstract::We examined the mechanisms that control the downregulation of the c-myc mRNA during differentiation of HL60 cells. On treatment with dimethyl sulfoxide, HL60 cells downmodulated their steady-state c-myc message levels, ceased to proliferate, and underwent terminal differentiation. In nuclear run-on assays in which dis...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.2.867

    authors: Siebenlist U,Bressler P,Kelly K

    更新日期:1988-02-01 00:00:00

  • The MES-1 murine enhancer element is closely associated with the heterogeneous 5' ends of two divergent transcription units.

    abstract::The location in the mouse genome of the 149-base pair MES-1 element, previously isolated by its ability to restore expression to an enhancerless selectable gene, was analyzed. The active moiety of the single-copy MES-1 element is located between the 5' ends of two divergent transcription units, SURF-1 and SURF-2, both...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.6.12.4558

    authors: Williams TJ,Fried M

    更新日期:1986-12-01 00:00:00

  • Overexpression of myogenin in muscles of transgenic mice: interaction with Id-1, negative crossregulation of myogenic factors, and induction of extrasynaptic acetylcholine receptor expression.

    abstract::To investigate the role of myogenin in regulating acetylcholine receptor expression in adult muscle, this muscle-specific basic helix-loop-helix transcription factor was overexpressed in transgenic mice by using regulatory elements conferring strong expression confined to differentiated postmitotic muscle fibers. Many...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.12.7127

    authors: Gundersen K,Rabben I,Klocke BJ,Merlie JP

    更新日期:1995-12-01 00:00:00

  • Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance.

    abstract::Simultaneous resistance to an array of drugs with different cytotoxic activities is a property of Saccharomyces cerevisiae, in which the protein Pdr3p has recently been shown to play a role as a transcriptional regulator. We provide evidence that the yeast PDR3 gene, which encodes a zinc finger transcription factor im...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.8.4043

    authors: Delahodde A,Delaveau T,Jacq C

    更新日期:1995-08-01 00:00:00

  • Structurally normal corneas in aldehyde dehydrogenase 3a1-deficient mice.

    abstract::We have constructed an ALDH3a1 null mouse to investigate the role of this enzyme that comprises nearly one-half of the total water-soluble protein in the mouse corneal epithelium. ALDH3a1-deficient mice are viable and fertile, have a corneal epithelium with a water-soluble protein content approximately half that of wi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.3.849-855.2002

    authors: Nees DW,Wawrousek EF,Robison WG Jr,Piatigorsky J

    更新日期:2002-02-01 00:00:00

  • Mutations in the zinc fingers of ADR1 that change the specificity of DNA binding and transactivation.

    abstract::ADR1 is a yeast transcription factor that contains two zinc fingers of the Cys-2-His-2 (C2H2) class. Mutations that change the specificity of DNA binding of ADR1 to its target site, upstream activation sequence 1 (UAS1), have been identified at three positions in the first zinc finger. Mutations Arg-115 to Gln, His-11...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.6.2784

    authors: Thukral SK,Morrison ML,Young ET

    更新日期:1992-06-01 00:00:00

  • Positive and negative autoregulation of REB1 transcription in Saccharomyces cerevisiae.

    abstract::Reb1p is a DNA binding protein of Saccharomyces cerevisiae that has been implicated in the activation of transcription by polymerase (Pol) II, in the termination of transcription by Pol I, and in the organization of nucleosomes. Studies of the transcriptional control of the REB1 gene have led us to identify three Reb1...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.7.4368

    authors: Wang KL,Warner JR

    更新日期:1998-07-01 00:00:00

  • Ig alpha and Ig beta are functionally homologous to the signaling proteins of the T-cell receptor.

    abstract::Signal transduction by antigen receptors and some Fc receptors requires the activation of a family of receptor-associated transmembrane accessory proteins. One common feature of the cytoplasmic domains of these accessory molecules is the presence is at least two YXXA repeats that are potential sites for interaction wi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.2.1095

    authors: Burkhardt AL,Costa T,Misulovin Z,Stealy B,Bolen JB,Nussenzweig MC

    更新日期:1994-02-01 00:00:00

  • Regulation of glycogen synthase kinase 3beta and downstream Wnt signaling by axin.

    abstract::Axin is a recently identified protein encoded by the fused locus in mice that is required for normal vertebrate axis formation. We have defined a 25-amino-acid sequence in axin that comprises the glycogen synthase kinase 3beta (GSK-3beta) interaction domain (GID). In contrast to full-length axin, which has been shown ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.10.7147

    authors: Hedgepeth CM,Deardorff MA,Rankin K,Klein PS

    更新日期:1999-10-01 00:00:00

  • Transposition of the yeast retroviruslike element Ty3 is dependent on the cell cycle.

    abstract::Host cell cycle genes provide important functions to retroviruses and retroviruslike elements. To define some of these functions, the cell cycle dependence of transposition of the yeast retroviruslike element Ty3 was examined. Ty3 is unique among retroviruslike elements because of the specificity of its integration, w...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.12.8229

    authors: Menees TM,Sandmeyer SB

    更新日期:1994-12-01 00:00:00

  • Bcl-2 retards cell cycle entry through p27(Kip1), pRB relative p130, and altered E2F regulation.

    abstract::Independent of its antiapoptotic function, Bcl-2 can, through an undetermined mechanism, retard entry into the cell cycle. Cell cycle progression requires the phosphorylation by cyclin-dependent kinases (Cdks) of retinoblastoma protein (pRB) family members to free E2F transcription factors. We have explored whether re...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.13.4745-4753.2000

    authors: Vairo G,Soos TJ,Upton TM,Zalvide J,DeCaprio JA,Ewen ME,Koff A,Adams JM

    更新日期:2000-07-01 00:00:00

  • New insights into the mechanism of inhibition of p53 by simian virus 40 large T antigen.

    abstract::Simian virus 40 (SV40) large tumor antigen (T antigen) has been shown to inhibit p53-dependent transcription by preventing p53 from binding to its cognate cis element. Data presented in this report provide the first direct functional evidence that T antigen, under certain conditions, may also repress p53-dependent tra...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.4.2746

    authors: Sheppard HM,Corneillie SI,Espiritu C,Gatti A,Liu X

    更新日期:1999-04-01 00:00:00

  • A role for VAMP8/endobrevin in surface deployment of the water channel aquaporin 2.

    abstract::Vesicle-associated-membrane protein 8 (VAMP8) is highly expressed in the kidney, but the exact physiological and molecular functions executed by this v-SNARE protein in nephrons remain elusive. Here, we show that the depletion of VAMP8 in mice resulted in hydronephrosis. Furthermore, the level of the vasopressin-respo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00814-09

    authors: Wang CC,Ng CP,Shi H,Liew HC,Guo K,Zeng Q,Hong W

    更新日期:2010-01-01 00:00:00

  • The Saccharomyces cerevisiae Nrd1-Nab3 transcription termination pathway acts in opposition to Ras signaling and mediates response to nutrient depletion.

    abstract::The Saccharomyces cerevisiae Nrd1-Nab3 pathway directs the termination and processing of short RNA polymerase II transcripts. Despite the potential for Nrd1-Nab3 to affect the transcription of both coding and noncoding RNAs, little is known about how the Nrd1-Nab3 pathway interacts with other pathways in the cell. Her...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00050-12

    authors: Darby MM,Serebreni L,Pan X,Boeke JD,Corden JL

    更新日期:2012-05-01 00:00:00

  • Id helix-loop-helix proteins antagonize pax transcription factor activity by inhibiting DNA binding.

    abstract::The Id subfamily of helix-loop-helix (HLH) proteins plays a fundamental role in the regulation of cellular proliferation and differentiation. The major mechanism by which Id proteins are thought to inhibit differentiation is through interaction with other HLH proteins and inhibition of their DNA-binding activity. Howe...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.2.524-533.2001

    authors: Roberts EC,Deed RW,Inoue T,Norton JD,Sharrocks AD

    更新日期:2001-01-01 00:00:00

  • Characterization of Sleeping Beauty transposition and its application to genetic screening in mice.

    abstract::The use of mutant mice plays a pivotal role in determining the function of genes, and the recently reported germ line transposition of the Sleeping Beauty (SB) transposon would provide a novel system to facilitate this approach. In this study, we characterized SB transposition in the mouse germ line and assessed its p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.24.9189-9207.2003

    authors: Horie K,Yusa K,Yae K,Odajima J,Fischer SE,Keng VW,Hayakawa T,Mizuno S,Kondoh G,Ijiri T,Matsuda Y,Plasterk RH,Takeda J

    更新日期:2003-12-01 00:00:00

  • Probing keratinocyte and differentiation specificity of the human K5 promoter in vitro and in transgenic mice.

    abstract::Keratins K5 and K14 form the extensive intermediate filament network of mitotically active basal cells in all stratified epithelia. We have explored the regulatory mechanisms governing cell-type-specific and differentiation stage-specific expression of the human K5 gene in transiently transfected keratinocytes in vitr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.6.3176

    authors: Byrne C,Fuchs E

    更新日期:1993-06-01 00:00:00

  • Characterization of a positive regulatory gene, LAC9, that controls induction of the lactose-galactose regulon of Kluyveromyces lactis: structural and functional relationships to GAL4 of Saccharomyces cerevisiae.

    abstract::Lactose or galactose induces the expression of the lactose-galactose regulon in Kluyveromyces lactis. We show here that the regulon is not induced in strains defective in LAC9. We demonstrate that this gene codes for a regulatory protein that acts in a positive manner to induce transcription. The LAC9 gene was isolate...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.7.3.1111

    authors: Wray LV Jr,Witte MM,Dickson RC,Riley MI

    更新日期:1987-03-01 00:00:00

  • DNA sequence requirements for transcriptional initiator activity in mammalian cells.

    abstract::A transcriptional initiator (Inr) for mammalian RNA polymerase II can be defined as a DNA sequence element that overlaps a transcription start site and is sufficient for (i) determining the start site location in a promoter that lacks a TATA box and (ii) enhancing the strength of a promoter that contains a TATA box. W...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.1.116

    authors: Javahery R,Khachi A,Lo K,Zenzie-Gregory B,Smale ST

    更新日期:1994-01-01 00:00:00

  • P-element-induced interallelic gene conversion of insertions and deletions in Drosophila melanogaster.

    abstract::We studied the process by which whd, a P-element insertion allele of the Drosophila melanogaster white locus, is replaced by its homolog in the presence of transposase. These events are interpreted as the result of double-strand gap repair following excision of the P transposon in whd. We used a series of alleles deri...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.11.7006

    authors: Johnson-Schlitz DM,Engels WR

    更新日期:1993-11-01 00:00:00

  • Extensive loss of heterozygosity is suppressed during homologous repair of chromosomal breaks.

    abstract::Loss of heterozygosity (LOH) is a common genetic alteration in tumors and often extends several megabases to encompass multiple genetic loci or even whole chromosome arms. Based on marker and karyotype analysis of tumor samples, a significant fraction of LOH events appears to arise from mitotic recombination between h...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.2.733-743.2003

    authors: Stark JM,Jasin M

    更新日期:2003-01-01 00:00:00

  • Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity.

    abstract::The GTPase-activating protein (GAP) stimulates the GTPase reaction of p21 by 5 orders of magnitude such that the kcat of the reaction is increased to 19 s-1. Mutations of residues in loop L1 (Gly-12 and Gly-13), in loop L2 (Thr-35 and Asp-38), and in loop L4 (Gln-61 and Glu-63) influence the reaction in different ways...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.5.2050

    authors: Gideon P,John J,Frech M,Lautwein A,Clark R,Scheffler JE,Wittinghofer A

    更新日期:1992-05-01 00:00:00

  • Stimulation of transcription factor binding and histone displacement by nucleosome assembly protein 1 and nucleoplasmin requires disruption of the histone octamer.

    abstract::To investigate the mechanisms by which transcription factors invade nucleosomal DNA and replace histones at control elements, we have examined the response of the histone octamer to transcription factor binding in the presence of histone-binding proteins (i.e., nucleosome assembly factors). We found that yeast nucleos...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.11.6178

    authors: Walter PP,Owen-Hughes TA,Côté J,Workman JL

    更新日期:1995-11-01 00:00:00

  • Clustering of Syk is sufficient to induce tyrosine phosphorylation and release of allergic mediators from rat basophilic leukemia cells.

    abstract::In mast cells, antigen-mediated aggregation of the high-affinity receptor for immunoglobulin E, Fc epsilon RI, stimulates tyrosine phosphorylation and activation of multiple signaling pathways leading to the release of several classes of mediators of the allergic response. Early events induced upon cross-linking of Fc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.15.3.1582

    authors: Rivera VM,Brugge JS

    更新日期:1995-03-01 00:00:00

  • Differential protein binding in lymphocytes to a sequence in the enhancer of the mouse retrovirus SL3-3.

    abstract::An electrophoretic mobility shift assay was used to characterize interactions of nuclear proteins with a DNA segment in the enhancer element of the leukemogenic murine retrovirus SL3-3. Mutation of a DNA sequence of the 5'-TGTGG-3' type decreased transcription in vivo specifically in T-lymphocyte cell lines. Extracts ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.4.1625

    authors: Thornell A,Hallberg B,Grundström T

    更新日期:1988-04-01 00:00:00

  • Dynamic histone variant exchange accompanies gene induction in T cells.

    abstract::Changes in chromatin composition are often a prerequisite for gene induction. Nonallelic histone variants have recently emerged as key players in transcriptional control and chromatin modulation. While the changes in chromatin accessibility and histone posttranslational modification (PTM) distribution that accompany g...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01590-08

    authors: Sutcliffe EL,Parish IA,He YQ,Juelich T,Tierney ML,Rangasamy D,Milburn PJ,Parish CR,Tremethick DJ,Rao S

    更新日期:2009-04-01 00:00:00

  • Isolation and structural characterization of the human 4F2 heavy-chain gene, an inducible gene involved in T-lymphocyte activation.

    abstract::The human 4F2 cell surface antigen is a 120-kilodalton (kDa) disulfide-linked heterodimer which is composed of an 80- to 90-kDa glycosylated heavy chain (4F2HC) and a 35- to 40-kDa nonglycosylated light chain (4F2LC). 4F2 belongs to a family of inducible cell surface molecules which are involved in T-lymphocyte activa...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.9.3809

    authors: Gottesdiener KM,Karpinski BA,Lindsten T,Strominger JL,Jones NH,Thompson CB,Leiden JM

    更新日期:1988-09-01 00:00:00