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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A newly recognized class of eukaryotic transcription factors is characterized by a bipartite sequence motif, consisting of a C-terminal dimerization region (the leucine zipper) and an N-terminal basic region (which mediates DNA binding). In studies of isolated leucine zipper peptides, the dimerization region has been characterized as a coiled coil of parallel alpha-helices. To extend these studies to a functional DNA-binding domain, we describe CD studies of the thermal unfolding and refolding of a 58-residue fragment of GCN4, the yeast homologue of the c-Jun protooncoprotein. This fragment, which contains the complete leucine zipper and basic region, retains the DNA-binding properties of the intact protein. The GCN4 DNA-binding domain exhibits two independent helix-coil unfolding transitions. The major transition (midpoint 65 degrees C) is due to dissociation of the dimer in accord with previous studies of an isolated leucine zipper. A novel pretransition in the temperature range 0-40 degrees C is also observed, which reflects partial stabilization of the nascent helix in the basic region. Remarkably, complete folding of the basic region as an alpha-helix requires specific DNA binding, and the protein-DNA complex exhibits a single cooperative unfolding transition. These results support a major feature of the recently proposed "scissor's grip" model of DNA recognition, in which the basic regions extend from the leucine zipper as bifurcating alpha-helical arms.
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PMID:Thermal unfolding studies of a leucine zipper domain and its specific DNA complex: implications for scissor's grip recognition. 226 59

Interleukin 3 (IL-3 or multi-colony-stimulating factor) plays an important role in the hematopoietic response to inflammatory stimuli through its action on both immature and mature blood cells. Like other lymphokines, IL-3 is produced in response to activation of the T-cell receptor and protein kinase C pathways. By using nuclear run-on assays of quiescent and stimulated T-cell lines, we demonstrate that IL-3 gene expression is controlled, at least in part, at the level of transcription. Functional reporter gene analysis was used to delineate two regions of the IL-3 5' flanking sequence responsible for transcriptional stimulation. DNA binding proteins that potentially mediate these responses were then recognized by mobility-shift and DNase footprinting assays. One region responsible for transcriptional enhancement was localized to the sequence GATGAATAAT, the cognate site of a transcription factor, here termed NF-IL3-A. A second region of functional activity and protein binding was localized to a single transcription factor AP-1 site. In addition three functionally inhibitory regions were identified. These results, along with the further characterization of NF-IL3-A, will contribute to the understanding of IL-3 gene regulation in stimulated T cells.
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PMID:Transcriptional regulation of interleukin 3 gene expression in T lymphocytes. 226 17

The cyclic AMP response element (CRE) is found in many cellular genes regulated by cyclic AMP, and similar elements are present in the early genes of adenovirus that are activated by E1A. The transcription factor CREB has previously been shown to bind this site, and cDNAs for CREB have recently been characterized. We report here the isolation of a cDNA encoding a human DNA-binding protein that also recognizes this motif in cellular and viral promoters. This protein, HB16, displays structural similarity to CREB and to c-Jun and c-Fos, which bind the related 12-O-tetradecanoylphorbol-13-acetate response element (TRE). HB16 contains a highly basic, putative DNA-binding domain and a leucine zipper structure thought to be involved in dimerization. Deletional analysis of HB16 demonstrated that the leucine zipper is required for its interaction with DNA. In addition, HB16 could form a complex with c-Jun but not with c-Fos. Despite its structural similarity to c-Jun and c-Fos and its interaction with c-Jun, HB16 had approximately a 10-fold-lower affinity for the TRE sequence than for the CRE sequence. Although HB16 and CREB both recognized the CRE motif, an extensive binding analysis of HB16 revealed differences in the fine specificity of binding of the two proteins. HB16 mRNA was found at various levels in many human tissues but was most abundant in brain, where its expression was widespread. The existence of more than one CRE-binding protein suggests that the CRE motif could serve multiple regulatory functions.
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PMID:A cDNA for a human cyclic AMP response element-binding protein which is distinct from CREB and expressed preferentially in brain. 232 2

fra-1 encodes a serum-inducible protein (Fra-1) that is antigenically related to Fos. We have characterized Fra-1 expression in serum-stimulated cells using antibodies raised against several regions of this protein. Fra-1, expressed transiently in COS cells or in serum-stimulated rat fibroblasts, undergoes extensive post-translational modification, primarily by phosphorylation of serine residues. It is present in both the nucleus and the cytoplasm and participates in a protein complex with Jun. Using proteins synthesized in reticulocyte lysates, we have shown that Fra-1, like Fos, binds to the AP-1 recognition element cooperatively with Jun. A truncated Fra-1 protein that contains the leucine zipper region but not an adjacent basic amino acid domain, complexes with Jun in vitro but fails to bind AP-1 oligonucleotides. These results demonstrate that Fra-1 contributes to the DNA-binding activity ascribed to transcription factor AP-1.
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PMID:The product of a fos-related gene, fra-1, binds cooperatively to the AP-1 site with Jun: transcription factor AP-1 is comprised of multiple protein complexes. 249 53

In an extensive screen of a cDNA library prepared from serum-stimulated mouse NIH 3T3 cells, we identified three distinct jun-related clones. Two of them were carrying c-jun and junB sequences respectively, whereas the sequence of the third group of clones (junD) was distinct from these two and from v-jun. The amino acid sequences derived from these jun-related clones are very well conserved in five distinct regions including the putative DNA binding domain. Truncated c-Jun and JunD proteins containing the C-terminus recognize the same DNA sequences which were defined as the PEA1/AP1 binding sequence or TPA response element (TRE). Furthermore, both can trans-activate a promoter including the TRE, and this activation is further enhanced by c-fos. Contrary to c-jun and junB transcription, which are strongly stimulated by serum or TPA treatment of quiescent 3T3 cells, junD transcription is not significantly stimulated in these conditions. The tissue distribution and levels of expression of junD mRNA differ from that of c-jun and junB mRNA. These observations suggest that each of these Jun-related gene products has a distinct role in the control of gene activity and growth in the organism.
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PMID:Characterization of junD: a new member of the jun proto-oncogene family. 250 80

c-jun is the cellular homologue of the recently isolated nuclear oncogene v-jun. This protooncogene encodes the cellular transcription factor AP-1. We have isolated the complementary DNA clone of rat c-jun mRNA. The rat c-jun complementary DNA clone encodes 334 amino acid residues, the sequence of which shows about 98, 96, and 81% homologies with mouse, human, and chicken c-jun products, respectively. The c-jun mRNA is highly expressed in the lung and slightly expressed in the brain. The amount of mRNA is even smaller in the liver and is not detected in the spleen. We have also determined c-jun expression during chemical hepatocarcinogenesis and demonstrated increased expression of mRNA in the precancerous lesion, hyperplastic nodules, as well as in the primary hepatocellular carcinomas.
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PMID:Structure and expression of the rat c-jun messenger RNA: tissue distribution and increase during chemical hepatocarcinogenesis. 250 34

The human proto-oncogene product, c-Jun, is a member of the AP-1 family of transcription factors, which mediate the regulation of gene expression in response to extracellular signaling. Comparison of c-Jun and v-Jun by in vitro transcription assays revealed that v-Jun has significantly greater transcriptional activity than c-Jun. Analysis of Jun mutants expressed in bacteria indicates that this difference in transcriptional activity is due to the presence of a regulatory domain located at the N-terminal region of c-Jun. Other Jun mutants identify an activation domain rich in acidic and proline residues toward the C-terminal end of the molecule, in a region near the DNA binding domain. These findings suggest that during retroviral transduction, a constitutively active Jun protein has been generated by deleting a negatively acting domain. This putative repressor domain may also play a role in the signal-dependent induction of c-Jun activity.
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PMID:Biochemical analysis of transcriptional activation by Jun: differential activity of c- and v-Jun. 251 Sep 34

Fos protein can trans-activate AP-1-dependent gene expression and trans-repress the c-fos promoter. Although we find that trans-repression is enhanced by coexpression of c-Jun, it does not require any of the AP-1 or ATF sites in the mouse c-fos promoter. A major target for repression is the serum response element (SRE). Fos mutants with an impaired leucine zipper are defective in trans-repression and transformation, suggesting that these functions involve the formation of Fos protein complexes. In contrast, mutations that abolish DNA binding of Fos enhance trans-repression but destroy the transforming potential of Fos. In addition, v-Fos protein efficiently transforms but is unable to trans-repress. These findings point to different mechanisms involved in trans-activation and trans-repression and suggest that trans-repression of the type described here is neither sufficient nor required for Fos-induced transformation.
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PMID:trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation. 251 30

The 35S promoter of the cauliflower mosaic virus (CaMV) contains a tandem repeat of the sequence TGACG in the region -83 to -63. This 21-base pair (bp) sequence, called as-1, is involved in root expression of the 35S promoter. When inserted in a promoter of a gene expressed specifically in photosynthetic tissues, as-1 confers high level expression in roots. We have described a factor, ASF-1, that binds specifically to as-1 in vitro. There is a good correlation between ASF-1 binding affinity to as-1 related sequences in vitro and the function of these sequences in vivo. These results strongly suggest that ASF-1 is responsible for the function of as-1. Here we report the isolation of tobacco complementary DNA clones encoding two TGACG-sequence-specific binding-proteins (TGA1a and TGA1b). Sequence analysis of the cDNA clones shows that both proteins contain a basic region that shows high homology to a stretch of basic amino acids in the nuclear factors CREB, GCN4, and c-Jun to a 'leucine-zipper' region. On the basis of binding specificity we propose TGA1a to be a good candidate for ASF-1.
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PMID:Two tobacco DNA-binding proteins with homology to the nuclear factor CREB. 252 73

We have investigated the mechanism of stimulation of thyroglobulin gene expression by thyrotropin (TSH) and cAMP in rat thyroid FRTL-5 cells. In contrast to the c-fos gene, induction of the thyroglobulin gene by TSH or cAMP is slow (10 h) and sensitive to cycloheximide treatment. We have identified a TSH and cAMP-responsive region of thyroglobulin gene between - 171 and - 140 base pairs from the transcription initiation site. The hormone-responsive region contains DNA sequence elements similar to the consensus cAMP-responsive element as well as the transcription factor AP-1-binding site but with opposite sequence polarity. Three DNA-protein complexes are formed when the hormone-responsive region is incubated with nuclear extracts of FRTL-5 cells. Formation of these complexes is dependent on TSH or cAMP stimulation, thus suggesting that the factors involved in binding to the hormone-responsive region may be induced by TSH. Although the identity of these factors is not yet known, they do not appear to be related to either cAMP-responsive element-binding protein or AP-1. These results suggest that thyroglobulin gene expression in FRTL-5 cells may be mediated by nuclear factors that are induced by cAMP in contrast to other genes (e.g. c-fos) whose activation involves post-translational modification of the pre-existing proteins specific for cAMP-responsive element.
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PMID:Induction of nuclear protein factors specific for hormone-responsive region during activation of thyroglobulin gene by thyrotropin in rat thyroid FRTL-5 cells. 254 Jan 96


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