Direct transcriptional stimulation of the ornithine decarboxylase gene by Fos in PC12 cells but not in fibroblasts.

Wrighton, C; Busslinger, Meinrad

doi:10.1128/mcb.13.8.4657

Cited by 56 publications

(36 citation statements)

References 46 publications

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“…c-fos is one of many genes that are induced rapidly after serum stimulation of cells in culture (28,43,57 (39,52,71,87). To determine whether the Fos-Jun complexes in L1-3c-fos cells were capable of activating transcription of these putative target genes, Northern hybridization analysis was performed.…”

Section: Methodsmentioning

confidence: 99%

Cell transformation by c-fos requires an extended period of expression and is independent of the cell cycle.

Miao¹,

Curran²

1994

Mol. Cell. Biol.

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The proto-oncogene transcription factors Fos and Jun form a heterodimeric complex that binds to DNA and regulates expression of specific target genes. Continuous expression of c-fos causes transformation of cultured fibroblasts and induces osteogenic sarcoma in mice. To investigate the molecular basis of fos-mediated oncogenesis, we developed a conditional cell transformation system in which Fos expression was regulated by isopropyl-o-D-thiogalactopyranoside (IPTG). Synthesis or repression of Fos in L1-3c-fos cells occurred rapidly, within 30 min, after the removal or addition of IPTG to the culture medium. However, there was a significant delay between the induction of Fos expression and the appearance of morphological transformation. No effect was observed after 12 h of Fos expression, partial transformation was detected after 24 h, and full transformation required approximately 3 days of continuous Fos expression. Similarly, the transformed cell morphology persisted for at least 2 days after repression of Fos, and a normal phenotype was observed only after 3 days. Fos-Jun complexes, capable of binding to AP-1 sequences, were present continuously during the delay in morphological transformation. Furthermore, increased expression of several candidate Fos target genes, including those encoding Fra-1, transin (stromelysin), collagenase, and ornithine decarboxylase, was detected shortly after Fos induction. The induction of morphological transformation was not dependent on the cell cycle, as it occurred in both cycling and noncycling cells. Thus, the Fos-Jun complexes present before L1-3c-fos cells become fully transformed are transcriptionally active. These complexes disappeared, and the Fos target genes were repressed at least 2 days prior to reversion. Our results suggest that cell transformation by Fos requires increased expression of a target gene(s) with a long-lived product(s) that must reach a critical level.

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Section: Methodsmentioning

confidence: 99%

Cell transformation by c-fos requires an extended period of expression and is independent of the cell cycle.

Miao¹,

Curran²

1994

Mol. Cell. Biol.

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“…The 940-bp PstI-EcoRI fragment was amplified by PCR with the two primers 5Ј-GCGCTGCAGATTC TTCTATATCTTCAAGATG-3Ј and 5Ј-GCGGAATTCTAAAATAAACTGA ACATCCATTA-3Ј. SP6 RNA transcripts of the three templates were in vitro translated in the presence of 3 H-labeled lysine (86 mCi/mmol; Amersham) in a nuclease-treated rabbit reticulocyte lysate as previously described (72). The protein products were analyzed by electrophoresis on an SDS-15% polyacrylamide gel, and the 3 H-labeled proteins were detected by sodium salicylate fluorography (16).…”

Section: Methodsmentioning

confidence: 99%

The Five Cleavage-Stage (CS) Histones of the Sea Urchin Are Encoded by a Maternally Expressed Family of Replacement Histone Genes: Functional Equivalence of the CS H1 and Frog H1M (B4) Proteins

Mandl

Brandt

Superti‐Furga

et al. 1997

Molecular and Cellular Biology

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The cleavage-stage (CS) histones of the sea urchin are known to be maternally expressed in the egg, have been implicated in chromatin remodeling of the male pronucleus following fertilization, and are the only histone variants present in embryonic chromatin up to the four-cell stage. With the help of partial peptide sequence information, we have isolated and identified CS H1, H2A, H2B, H3, and H4 cDNAs from egg poly(A) ؉ mRNA of the sea urchin Psammechinus miliaris. All five CS proteins correspond to replacement histone variants which are encoded by replication-independent genes containing introns, poly(A) addition signals, and long nontranslated sequences. Transcripts of the CS histone genes could be detected only during oogenesis and in development up to the early blastula stage. The CS proteins, with the exception of H4, are unique histones which are distantly related in sequence to the early, late, and sperm histone subtypes of the sea urchin. In contrast, the CS H1 protein displays highest sequence homology with the H1M (B4) histone of Xenopus laevis. Both H1 proteins are replacement histone variants with very similar developmental expression profiles in their respective species, thus indicating that the frog H1M (B4) gene is a vertebrate homolog of the CS H1 gene. These data furthermore suggest that the CS histones are of ancient evolutionary origin and may perform similar conserved functions during oogenesis and early development in different species.Histones are basic proteins that associate with each other and nuclear DNA to form the nucleosome. This basic unit of chromatin consists of two molecules each of the core histones H2A, H2B, H3, and H4, while the H1 protein interacts both with the histone octamer and with linker DNA and is responsible for packaging nucleosomes into higher-order structures. The core histones H3 and H4 are almost invariant in evolution. The less well conserved H2A and H2B proteins often occur as different subtypes within the same organism, while the H1 protein is the most variable of all histones (reviewed in reference 66).The expression of the majority of histone genes is tightly coupled to DNA synthesis by specific transcriptional and posttranscriptional mechanisms. These so-called replication histone genes code for mRNAs with short 5Ј and 3Ј untranslated regions; they lack introns and polyadenylation sequences but instead end in a 3Ј-terminal palindrome (11, 34) that serves as a recognition sequence for U7 snRNP-mediated 3Ј processing of histone pre-mRNA (5). A minor group of histone genes is expressed at a basal level throughout the cell cycle in proliferating cells and at a reduced but significant rate in quiescent cells, where their proteins gradually replace the replicationdependent histones in the chromatin (73, 74). These so-called replacement histone genes contain introns, code for polyadenylated mRNA with long untranslated sequences, and are thus classical RNA polymerase II transcription units (9,22,68).The sea urchin genome contains four distinct histone gene familie...

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“…Deregulated expression of ODC and the subsequent changes in polyamine concentrations have been associated with several types of tumors (4, 8 -10). Recent studies indicate that overexpression of oncogenes such as myc (11)(12)(13), ras (14), fos (15), and mos (16) result in elevated levels of ODC expression. Importantly, two studies have shown that overexpression of ODC in fibroblasts induces neoplastic transformation and suggest a direct link between deregulation of ODC expression and oncogenesis (17,18).…”

mentioning

confidence: 99%

Transcription Factor ZBP-89 Regulates the Activity of the Ornithine Decarboxylase Promoter

Law¹,

Itoh²,

Law³

et al. 1998

Journal of Biological Chemistry

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Appropriate cellular levels of polyamines are required for cell growth and differentiation. Ornithine decarboxylase is a key regulatory enzyme in the biosynthesis of polyamines, and precise regulation of the expression of this enzyme is required, according to cellular growth state. A variety of mitogens increase the level of ornithine decarboxylase activity, and, in most cases, this elevation is due to increased levels of mRNA. A GC box in the proximal promoter of the ornithine decarboxylase gene is required for basal and induced transcriptional activity, and two proteins, Sp1 and NF-ODC 1 , bind to this region in a mutually exclusive manner. Polyamines are essential cations for normal cell growth and differentiation (1, 2). Increased synthesis of these compounds is closely associated with, and necessary for, stimulated cell proliferation and tumor promotion. Tight regulation of polyamine biosynthesis is important as overproduction of these compounds can be toxic to cells (3, 4). Ornithine decarboxylase (ODC) 1 catalyzes a key regulated step in polyamine synthesis, and regulation of ODC activity is a major mechanism for controlling polyamine concentrations within cells. The activity of this enzyme is tightly regulated during normal cell growth and differentiation. An increase in ODC activity is required for reentry of quiescent cells into the cell cycle (2, 5-7). Deregulated expression of ODC and the subsequent changes in polyamine concentrations have been associated with several types of tumors (4, 8 -10). Recent studies indicate that overexpression of oncogenes such as myc (11-13), ras (14), fos (15), and mos (16) result in elevated levels of ODC expression. Importantly, two studies have shown that overexpression of ODC in fibroblasts induces neoplastic transformation and suggest a direct link between deregulation of ODC expression and oncogenesis (17,18).Both activation and inhibition of ODC activity is required for precise regulation of ODC levels. A broad spectrum of stimuli, including hormones, growth factors, tumor promoters and oncogenes elevates ODC activity in the cell. In most cases, these increases in activity result from enhanced levels of ODC mRNA (6, 7). Several of the DNA elements and protein factors involved in both basal and stimulated activity of the ODC promoter have been identified, including several binding sites for transcription factor Sp1, two binding sites for members of the CREB/ ATF family of transcription factors, and binding sites for transcription factors related to c-myc (7). Little is known about DNA elements or protein factors that are involved in repressing ODC transcription. A GC-rich region located at Ϫ123 to Ϫ91 relative to the transcriptional start site of the ODC promoter seems to be such an element. We have demonstrated that two proteins bind this site in a mutually exclusive manner, Sp1 and NF-ODC 1 (19). Sp1 is a well characterized transcription factor that is found in most eukaryotic cell and is directly involved in both basal and induced expression of many genes. NF-O...

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Direct transcriptional stimulation of the ornithine decarboxylase gene by Fos in PC12 cells but not in fibroblasts.

Cited by 56 publications

References 46 publications

Cell transformation by c-fos requires an extended period of expression and is independent of the cell cycle.

Cell transformation by c-fos requires an extended period of expression and is independent of the cell cycle.

The Five Cleavage-Stage (CS) Histones of the Sea Urchin Are Encoded by a Maternally Expressed Family of Replacement Histone Genes: Functional Equivalence of the CS H1 and Frog H1M (B4) Proteins

Transcription Factor ZBP-89 Regulates the Activity of the Ornithine Decarboxylase Promoter

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