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Michael J. Birrer - One of the best experts on this subject based on the ideXlab platform.

  • Cyclin a is a C-Jun target gene and is necessary for C-Jun-induced anchorage-independent growth in RAT1a cells
    Journal of Biological Chemistry, 2005
    Co-Authors: Motoo Katabami, Howard Donninger, Fumihiro Hommura, Virna D. Leaner, Ichiro Kinoshita, Jeffrey F. B. Chick, Michael J. Birrer
    Abstract:

    Abstract Overexpression of C-Jun enables Rat1a cells to grow in an anchorage-independent manner. We used an inducible C-Jun system under the regulation of doxycycline in Rat1a cells to identify potential C-Jun target genes necessary for C-Jun-induced anchorage-independent growth. Induction of C-Jun results in sustained expression of cyclin A in the nonadherent state with only minimal expression in the absence of C-Jun. The promoter activity of cyclin A2 was 4-fold higher in Rat1a cells in which C-Jun expression was induced compared with the control cells. Chromatin immunoprecipitation demonstrated that C-Jun bound directly to the cyclin A2 promoter. Mutation analysis of the cyclin A2 promoter mapped the C-Jun regulatory site to an ATF site at position –80. C-Jun was able to bind to this site both in vitro and in vivo, and mutation of this site completely abolished promoter activity. Cyclin A1 was also elevated in C-Jun-overexpressing Rat1a cells; however, C-Jun did not regulate this gene directly, since it did not bind directly to the cyclin A1 promoter. Suppression of cyclin A expression via the introduction of a cyclin A antisense sequences significantly reduced the ability of C-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. Taken together, these results suggest that cyclin A is a target of C-Jun and is necessary but not sufficient for C-Jun-induced anchorage-independent growth. In addition, we demonstrated that the cytoplasmic oncogenes Ras and Src transcriptionally activated the cyclin A2 promoter via the ATF site at position –80. Using a dominant negative C-Jun mutant, TAM67, we showed that this transcriptional activation of cyclin A2 requires C-Jun. Thus, our results suggest that C-Jun is a mediator of the aberrant cyclin A2 expression associated with Ras/Src-induced transformation.

  • hmg i y is a c jun activator protein 1 target gene and is necessary for c jun induced anchorage independent growth in rat1a cells
    Molecular Cancer Research, 2004
    Co-Authors: Fumihiro Hommura, Motoo Katabami, Howard Donninger, Virna D. Leaner, Takita Felder Sumter, Linda M S Resar, Michael J. Birrer
    Abstract:

    The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible C-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by C-Jun. Following induction of C-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of C-Jun expression, and gel mobility shift assays demonstrate that induced C-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of C-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing C-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of C-Jun necessary for C-Jun–induced anchorage-independent growth in Rat1a cells.

  • HMG-I/Y is a C-Jun/activator protein-1 target gene and is necessary for C-Jun-induced anchorage-independent growth in Rat1a cells.
    Molecular Cancer Research, 2004
    Co-Authors: Fumihiro Hommura, Motoo Katabami, Howard Donninger, Virna D. Leaner, Takita Felder Sumter, Linda M S Resar, Michael J. Birrer
    Abstract:

    The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible C-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by C-Jun. Following induction of C-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of C-Jun expression, and gel mobility shift assays demonstrate that induced C-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of C-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing C-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of C-Jun necessary for C-Jun–induced anchorage-independent growth in Rat1a cells.

  • C-Jun Triggers Apoptosis in Human Vascular Endothelial Cells
    Circulation Research, 1999
    Co-Authors: Nanping Wang, Michael J. Birrer, Lynne Verna, Stephen Hardy, Kuo-sheng Ma, Michael B. Stemerman
    Abstract:

    Abstract —In endothelial cells (ECs), the transcription factor C-Jun is induced by a variety of stimuli that perturb EC function. To extend our understanding of the role of C-Jun in EC physiology, we have directed overexpression of C-Jun in human umbilical vein ECs by using a tetracycline-regulated adenoviral expression system. In this study, we report a novel observation using this system. Specific expression of C-Jun is a sufficient trigger for ECs to undergo apoptosis, as demonstrated by a set of combined assays including an ELISA specific for histone-associated DNA fragmentation, DNA laddering, and TdT-mediated dUTP nick end labeling (TUNEL). Tetracycline can effectively shut off C-Jun overexpression and prevent EC apoptosis. Cleavage of poly(ADP-ribose) polymerase was also detected in ECs overexpressing C-Jun. Moreover, inhibitors of cysteine proteases blocked the apoptosis, suggesting a caspase-associated mechanism involved in proapoptotic effects of C-Jun. To gain further insight into the role of C-Jun as a pathophysiological regulator of EC death, TAM67, a dominant-negative mutant of C-Jun, was overexpressed in human umbilical vein ECs to abrogate endogenous C-Jun/activator protein-1 activation. H 2 O 2 -triggered apoptosis was largely attenuated in ECs overexpressing TAM67. Together, these results suggest that C-Jun, as a proapoptotic molecule, may play a role in mediating the cell death program in vascular endothelium.

  • Identification of domains of C-Jun mediating androgen receptor transactivation.
    Oncogene, 1998
    Co-Authors: Scott C. Wise, Michael J. Birrer, Lori A. Burmeister, Xiaofeng Zhou, Athanasios Bubulya, Jennifer L. Oberfield, Lirim Shemshedini
    Abstract:

    : The proto-oncoprotein C-Jun, when complexed with c-Fos, forms the climeric complex identified as AP-1 which regulates transcription directly by binding to AP-1-responsive genes. We have previously reported an indirect mechanism by which C-Jun is able to regulate transcription by stimulating androgen receptor transactivation in the absence of c-Fos or any apparent DNA binding. A series of C-Jun mutants were tested in order to characterize the domains of C-Jun responsible for this effect. The studies reported here indicate that a functional bZIP region and a portion of the N-terminal activation functions is necessary for C-Jun stimulation of androgen receptor transactivation. Testing C-Jun/v-Jun chimeras, we show that v-Jun is unable to stimulate androgen receptor transactivation and the effect is dependent on the C-Jun activation functions. C-Jun exhibits a bell-shaped activity on androgen receptor-mediated transactivation which appears to be distinct from C-Jun's transactivation ability. A C-Jun mutant deficient in transactivation is able to stimulate androgen receptor activity. These results indicate that C-Jun's transactivation ability can be separated from C-Jun's ability to stimulate the androgen receptor transactivation.

Fumihiro Hommura - One of the best experts on this subject based on the ideXlab platform.

  • Cyclin a is a C-Jun target gene and is necessary for C-Jun-induced anchorage-independent growth in RAT1a cells
    Journal of Biological Chemistry, 2005
    Co-Authors: Motoo Katabami, Howard Donninger, Fumihiro Hommura, Virna D. Leaner, Ichiro Kinoshita, Jeffrey F. B. Chick, Michael J. Birrer
    Abstract:

    Abstract Overexpression of C-Jun enables Rat1a cells to grow in an anchorage-independent manner. We used an inducible C-Jun system under the regulation of doxycycline in Rat1a cells to identify potential C-Jun target genes necessary for C-Jun-induced anchorage-independent growth. Induction of C-Jun results in sustained expression of cyclin A in the nonadherent state with only minimal expression in the absence of C-Jun. The promoter activity of cyclin A2 was 4-fold higher in Rat1a cells in which C-Jun expression was induced compared with the control cells. Chromatin immunoprecipitation demonstrated that C-Jun bound directly to the cyclin A2 promoter. Mutation analysis of the cyclin A2 promoter mapped the C-Jun regulatory site to an ATF site at position –80. C-Jun was able to bind to this site both in vitro and in vivo, and mutation of this site completely abolished promoter activity. Cyclin A1 was also elevated in C-Jun-overexpressing Rat1a cells; however, C-Jun did not regulate this gene directly, since it did not bind directly to the cyclin A1 promoter. Suppression of cyclin A expression via the introduction of a cyclin A antisense sequences significantly reduced the ability of C-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. Taken together, these results suggest that cyclin A is a target of C-Jun and is necessary but not sufficient for C-Jun-induced anchorage-independent growth. In addition, we demonstrated that the cytoplasmic oncogenes Ras and Src transcriptionally activated the cyclin A2 promoter via the ATF site at position –80. Using a dominant negative C-Jun mutant, TAM67, we showed that this transcriptional activation of cyclin A2 requires C-Jun. Thus, our results suggest that C-Jun is a mediator of the aberrant cyclin A2 expression associated with Ras/Src-induced transformation.

  • hmg i y is a c jun activator protein 1 target gene and is necessary for c jun induced anchorage independent growth in rat1a cells
    Molecular Cancer Research, 2004
    Co-Authors: Fumihiro Hommura, Motoo Katabami, Howard Donninger, Virna D. Leaner, Takita Felder Sumter, Linda M S Resar, Michael J. Birrer
    Abstract:

    The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible C-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by C-Jun. Following induction of C-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of C-Jun expression, and gel mobility shift assays demonstrate that induced C-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of C-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing C-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of C-Jun necessary for C-Jun–induced anchorage-independent growth in Rat1a cells.

  • HMG-I/Y is a C-Jun/activator protein-1 target gene and is necessary for C-Jun-induced anchorage-independent growth in Rat1a cells.
    Molecular Cancer Research, 2004
    Co-Authors: Fumihiro Hommura, Motoo Katabami, Howard Donninger, Virna D. Leaner, Takita Felder Sumter, Linda M S Resar, Michael J. Birrer
    Abstract:

    The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible C-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by C-Jun. Following induction of C-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of C-Jun expression, and gel mobility shift assays demonstrate that induced C-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of C-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing C-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of C-Jun necessary for C-Jun–induced anchorage-independent growth in Rat1a cells.

Motoo Katabami - One of the best experts on this subject based on the ideXlab platform.

  • Cyclin a is a C-Jun target gene and is necessary for C-Jun-induced anchorage-independent growth in RAT1a cells
    Journal of Biological Chemistry, 2005
    Co-Authors: Motoo Katabami, Howard Donninger, Fumihiro Hommura, Virna D. Leaner, Ichiro Kinoshita, Jeffrey F. B. Chick, Michael J. Birrer
    Abstract:

    Abstract Overexpression of C-Jun enables Rat1a cells to grow in an anchorage-independent manner. We used an inducible C-Jun system under the regulation of doxycycline in Rat1a cells to identify potential C-Jun target genes necessary for C-Jun-induced anchorage-independent growth. Induction of C-Jun results in sustained expression of cyclin A in the nonadherent state with only minimal expression in the absence of C-Jun. The promoter activity of cyclin A2 was 4-fold higher in Rat1a cells in which C-Jun expression was induced compared with the control cells. Chromatin immunoprecipitation demonstrated that C-Jun bound directly to the cyclin A2 promoter. Mutation analysis of the cyclin A2 promoter mapped the C-Jun regulatory site to an ATF site at position –80. C-Jun was able to bind to this site both in vitro and in vivo, and mutation of this site completely abolished promoter activity. Cyclin A1 was also elevated in C-Jun-overexpressing Rat1a cells; however, C-Jun did not regulate this gene directly, since it did not bind directly to the cyclin A1 promoter. Suppression of cyclin A expression via the introduction of a cyclin A antisense sequences significantly reduced the ability of C-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. Taken together, these results suggest that cyclin A is a target of C-Jun and is necessary but not sufficient for C-Jun-induced anchorage-independent growth. In addition, we demonstrated that the cytoplasmic oncogenes Ras and Src transcriptionally activated the cyclin A2 promoter via the ATF site at position –80. Using a dominant negative C-Jun mutant, TAM67, we showed that this transcriptional activation of cyclin A2 requires C-Jun. Thus, our results suggest that C-Jun is a mediator of the aberrant cyclin A2 expression associated with Ras/Src-induced transformation.

  • hmg i y is a c jun activator protein 1 target gene and is necessary for c jun induced anchorage independent growth in rat1a cells
    Molecular Cancer Research, 2004
    Co-Authors: Fumihiro Hommura, Motoo Katabami, Howard Donninger, Virna D. Leaner, Takita Felder Sumter, Linda M S Resar, Michael J. Birrer
    Abstract:

    The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible C-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by C-Jun. Following induction of C-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of C-Jun expression, and gel mobility shift assays demonstrate that induced C-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of C-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing C-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of C-Jun necessary for C-Jun–induced anchorage-independent growth in Rat1a cells.

  • HMG-I/Y is a C-Jun/activator protein-1 target gene and is necessary for C-Jun-induced anchorage-independent growth in Rat1a cells.
    Molecular Cancer Research, 2004
    Co-Authors: Fumihiro Hommura, Motoo Katabami, Howard Donninger, Virna D. Leaner, Takita Felder Sumter, Linda M S Resar, Michael J. Birrer
    Abstract:

    The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible C-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by C-Jun. Following induction of C-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of C-Jun expression, and gel mobility shift assays demonstrate that induced C-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of C-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing C-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of C-Jun necessary for C-Jun–induced anchorage-independent growth in Rat1a cells.

Michael Karin - One of the best experts on this subject based on the ideXlab platform.

  • Lasting N-Terminal Phosphorylation of C-Jun and Activation of C-Jun N-Terminal Kinases after Neuronal Injury
    The Journal of Neuroscience, 1998
    Co-Authors: Thomas Herdegen, Francois Xavier Claret, Tuula Kallunki, Ana Martin-villalba, Christine Winter, Tony Hunter, Michael Karin
    Abstract:

    Transcription factor C-Jun is proposed to control neuronal cell death and survival, but its activation by N-terminal phosphorylation and the underlying activity of the C-Jun N-terminal kinases (JNKs) remain to be elucidated in the adult mammalian brain. We generated a polyclonal antiserum that specifically recognizes C-Jun phosphorylated at its serine 73 (S73) residue after UV irradiation of 3T3 cells. Disruption of the C-Jun locus in 3T3 cells abolished this reaction, and retransfection of the human C-Jun at the C-Jun−/− background restored it. The phospho-C-Jun antiserum was used to visualize N-terminally phosphorylated C-Jun in the adult rat brain with cellular resolution. Prolonged C-Jun S73 phosphorylation was detected in affected neurons up to 5 d after transient occlusion of medial cerebral artery or up to 50 d after transection of central nerve fiber tracts. After cerebral ischemia–reperfusion, phosphorylation of C-Jun was linked with induced expression of Fas-ligand (APO-1, CD95-ligand), whose gene is a putative C-Jun/AP-1 target, and with terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) reactivity, a marker for apoptosis. After nerve fiber transection, however, lasting C-Jun phosphorylation occurred in axotomized neurons negative for Fas-ligand or TUNEL and regardless of degeneration or survival. In contrast to these lasting phosphorylation patterns, transient seizure activity by pentylenetetrazole provoked only a brief C-Jun phosphorylation and JNK activation. In extracts from ischemic or axotomized brain compartments, C-Jun phosphorylation correlated with enhanced long-term JNK activity, and in-gel kinase assays visualized proteins with sizes corresponding to JNK isoforms as the only C-Jun N-terminally phosphorylating enzymes. These results demonstrate that lasting C-Jun S73 phosphorylation and JNK activity are part of neuronal stress response after neurodegenerative disorders in the adult mammalian brain with Fas-ligand as a putative apoptotic effector.

  • identification of an oncoprotein and uv responsive protein kinase that binds and potentiates the c jun activation domain
    Genes & Development, 1993
    Co-Authors: Masahiko Hibi, Tod Smeal, Audrey Minden, Michael Karin
    Abstract:

    The activity of C-Jun is regulated by phosphorylation. Various stimuli including transforming oncogenes and UV light, induce phosphorylation of serines 63 and 73 in the amino-terminal activation domain of C-Jun and thereby potentiate its trans-activation function. We identified a serine/threonine kinase whose activity is stimulated by the same signals that stimulate the amino-terminal phosphorylation of C-Jun. This novel C-Jun amino-terminal kinase (JNK), whose major form is 46 kD, binds to a specific region within the C-Jun trans-activation domain and phosphorylates serines 63 and 73. Phosphorylation results in dissociation of the C-Jun-JNK complex. Mutations that disrupt the kinase-binding site attenuate the response of C-Jun to Ha-Ras and UV

  • JunB differs from C-Jun in its DNA-binding and dimerization domains, and represses C-Jun by formation of inactive heterodimers.
    Genes & Development, 1993
    Co-Authors: Tiliang Deng, Michael Karin
    Abstract:

    : JunB differs considerably from C-Jun in its ability to activate AP-1-responsive genes and induce oncogenic transformation. We demonstrate that the decreased ability of JunB to activate gene expression is the result of a small number of amino acid changes between its DNA-binding and dimerization motifs and the corresponding regions of C-Jun. These changes lead to a 10-fold decrease in the DNA-binding activity of JunB. JunB can be converted into a C-Jun-like activator by substituting four amino acids in its DNA-binding and dimerization motifs with the corresponding C-Jun sequences. JunB can also attenuate trans-activation by C-Jun, an activity mediated by its leucine zipper. This ability depends on two glycine residues that decrease the stability of the JunB leucine zipper, resulting in decreased homodimerization and increased heterodimerization. These results illustrate how small changes in primary structure, including chemically conservative changes, can result in functional divergence of two highly related transcriptional regulators.

Howard Donninger - One of the best experts on this subject based on the ideXlab platform.

  • Cyclin a is a C-Jun target gene and is necessary for C-Jun-induced anchorage-independent growth in RAT1a cells
    Journal of Biological Chemistry, 2005
    Co-Authors: Motoo Katabami, Howard Donninger, Fumihiro Hommura, Virna D. Leaner, Ichiro Kinoshita, Jeffrey F. B. Chick, Michael J. Birrer
    Abstract:

    Abstract Overexpression of C-Jun enables Rat1a cells to grow in an anchorage-independent manner. We used an inducible C-Jun system under the regulation of doxycycline in Rat1a cells to identify potential C-Jun target genes necessary for C-Jun-induced anchorage-independent growth. Induction of C-Jun results in sustained expression of cyclin A in the nonadherent state with only minimal expression in the absence of C-Jun. The promoter activity of cyclin A2 was 4-fold higher in Rat1a cells in which C-Jun expression was induced compared with the control cells. Chromatin immunoprecipitation demonstrated that C-Jun bound directly to the cyclin A2 promoter. Mutation analysis of the cyclin A2 promoter mapped the C-Jun regulatory site to an ATF site at position –80. C-Jun was able to bind to this site both in vitro and in vivo, and mutation of this site completely abolished promoter activity. Cyclin A1 was also elevated in C-Jun-overexpressing Rat1a cells; however, C-Jun did not regulate this gene directly, since it did not bind directly to the cyclin A1 promoter. Suppression of cyclin A expression via the introduction of a cyclin A antisense sequences significantly reduced the ability of C-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. Taken together, these results suggest that cyclin A is a target of C-Jun and is necessary but not sufficient for C-Jun-induced anchorage-independent growth. In addition, we demonstrated that the cytoplasmic oncogenes Ras and Src transcriptionally activated the cyclin A2 promoter via the ATF site at position –80. Using a dominant negative C-Jun mutant, TAM67, we showed that this transcriptional activation of cyclin A2 requires C-Jun. Thus, our results suggest that C-Jun is a mediator of the aberrant cyclin A2 expression associated with Ras/Src-induced transformation.

  • hmg i y is a c jun activator protein 1 target gene and is necessary for c jun induced anchorage independent growth in rat1a cells
    Molecular Cancer Research, 2004
    Co-Authors: Fumihiro Hommura, Motoo Katabami, Howard Donninger, Virna D. Leaner, Takita Felder Sumter, Linda M S Resar, Michael J. Birrer
    Abstract:

    The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible C-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by C-Jun. Following induction of C-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of C-Jun expression, and gel mobility shift assays demonstrate that induced C-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of C-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing C-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of C-Jun necessary for C-Jun–induced anchorage-independent growth in Rat1a cells.

  • HMG-I/Y is a C-Jun/activator protein-1 target gene and is necessary for C-Jun-induced anchorage-independent growth in Rat1a cells.
    Molecular Cancer Research, 2004
    Co-Authors: Fumihiro Hommura, Motoo Katabami, Howard Donninger, Virna D. Leaner, Takita Felder Sumter, Linda M S Resar, Michael J. Birrer
    Abstract:

    The transcription complex activator protein-1 (AP-1) plays a role in a diverse number of cellular processes including proliferation, differentiation, and apoptosis. To identify AP-1–responsive target genes, we used a doxycycline-inducible C-Jun system in Rat1a cells. The HMG-I/Y chromatin binding protein was found to be up-regulated by C-Jun. Following induction of C-Jun expression, Rat1a cells under nonadherent growth conditions have sustained HMG-I/Y mRNA expression and 2-fold higher protein than uninduced cells. HMG-I/Y promoter reporter assays show that HMG-I/Y promoter activity increases in the presence of C-Jun expression, and gel mobility shift assays demonstrate that induced C-Jun binds to an AP-1 consensus site at position −1,091 in the HMG-I/Y promoter. Suppression of HMG-I/Y expression by its antisense sequence significantly reduces the ability of C-Jun–overexpressing Rat1a cells to grow in an anchorage-independent fashion. HMG-I/Y transforms Rat1a cells (although the colonies are smaller than that observed for the cells overexpressing C-Jun). Taken together, these results suggest that HMG-I/Y is a direct transcriptional target of C-Jun necessary for C-Jun–induced anchorage-independent growth in Rat1a cells.