Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two octanucleotide binding protein factors (mOct-1 and mOct-2A) are detected in nuclear extracts of lymphoid NS/0 cell line. These proteins, corresponding to human Oct-1 and Oct-2A nuclear factors, were purified by ion exchange and heparin-agarose chromatography. With retardation assay technique it was shown that mOct-2A factor at all steps of purification contains tightly bound protein, dissociating in the presence of a nonspecific native DNA. This octa-protein-associated factor (OAF) has low affinity to DNA and is not able to bind specifically the promoter of kappa-gene. However it interacts with DNA together with mOct-2A in highly specific manner but does not form complexes with mOct-1 and mOct-2B factors. Since OAF can be attached specifically only to mOct-2A (which play an essential role in initiation of kappa-gene transcription) this attachment may be considered as necessary for its recognition as a specific transcription factor. The ability of OAF like alpha TIF factor (specifically interacting with Oct-1) to discriminate between the Oct proteins, recognizing the same cis-acting oct-elements, shows how the non-DNA-binding transcription factors can influence differentially the transcription by two proteins binding to the same DNA sequences.
Mol Biol (Mosk)
PMID:[Proteins, interacting with the promotor of the immunoglobulin kappa gene]. 824 25

In the mouse mammary tumor virus promoter, a tandem of octamer motifs, recognized by ubiquitous and tissue-restricted Oct transcription factors, is located upstream of the TATA box and next to a binding site for the transcription factor nuclear factor I (NF-I). Their function was investigated with mutant long terminal repeats under different transfection conditions in mouse Ltk- cells and quantitative S1 nuclease mapping of the transcripts. In stable transfectants, which are most representative of the state of proviral DNA with respect to both number of integrated DNA templates and chromatin organization, a long terminal repeat mutant of both octamer sites showed an average 50-fold reduction of the basal transcription level, while the dexamethasone-stimulated level was unaffected. DNase I in vitro footprinting assays with L-cell nuclear protein extracts showed that the mutant DNA was unable to bind octamer factors but had a normal footprint in the NF-I site. I conclude that mouse mammary tumor virus employs the tandem octamer motifs of the viral promoter, recognized by the ubiquitous transcription factor Oct-1, for its basal transcriptional activity and the NF-I binding site, as previously shown, for glucocorticoid-stimulated transcription. A deletion mutant with only one octamer site showed a marked base-level reduction at high copy number but little reduction at low copies of integrated plasmids. The observed transcription levels may depend both on the relative ratio of transcription factors to DNA templates and on the relative affinity of binding sites, as determined by oligonucleotide competition footprinting.
Mol Cell Biol 1994 Feb
PMID:Stably integrated mouse mammary tumor virus long terminal repeat DNA requires the octamer motifs for basal promoter activity. 828

The promoters of vertebrate U6 small nuclear RNA genes contain a distal control region whose presence results in at least an eightfold level of transcriptional activation in vivo. Previous transfection experiments have demonstrated that most of the distal control region of a human U6 gene resides in a restriction fragment located from -244 to -149 relative to the transcriptional start site. Three octamer-related motifs that bind recombinant Oct-1 transcription factor in vitro exist in this segment of DNA. However, transfection of human 293 cells with various plasmid templates in which these Oct-1 binding sites had been disrupted individually or in combination showed that only the consensus octamer motif located between positions -221 to -214 was functional. Even so, the consensus octamer motif mutant template was expressed at only a moderately reduced level relative to the wild-type promoter. When another octamer-related sequence located nearby, one that did not bind Oct-1 in vitro, was disrupted along with the perfect octamer site, expression was reduced fivefold in transfected cells. A factor that binds this functional, nonconsensus octamer site (NONOCT) was detected in crude cellular extracts. However, the NONOCT sequence was not essential for activation, since its disruption caused only a 40% reduction in U6 gene expression, and mutagenesis to convert the NONOCT sequence to a consensus octamer motif restored wild-type expression. Furthermore, in vitro transcription of a human U6 proximal promoter joined to a single copy of the octamer motif was stimulated by the addition of recombinant Oct-1 protein.
Mol Cell Biol 1993 Aug
PMID:Functional characterization of elements in a human U6 small nuclear RNA gene distal control region. 833 8

At least three stages in the intrathymic development of pre-T cells are demarcated by differences in the competence to express the interleukin-2 (IL-2) gene as an acute response to stimulation. IL-2 inducibility appears to be acquired relatively early, prior to T-cell receptor (TcR) gene rearrangement. It is then abrogated during the stage when cells are subject to positive and negative selection, i.e., the fate determination processes that select cells for maturation or death. IL-2 inducibility finally reappears in mature classes of thymocytes that have undergone positive selection. To provide a basis for a molecular explanation of these developmental transitions, we have examined the representation in different thymocyte subsets of a set of DNA-binding proteins implicated in IL-2 gene regulation. As the DNA-binding activities of many factors are elicited only by inductive stimuli, the cells were cultured in the presence or absence of the calcium ionophore A23187 and phorbol ester. Our results separate these factors into four regulatory classes: (i) constitutive factors, such as Oct-1 and probably Sp1, that are expressed in thymocytes at all stages; (ii) inducible factors, such as NF-kappa B and complexes binding to the region of a CD28 response element, that can be activated in all thymocytes, including those cells (CD4+ CD8+ TcRlow) that can undergo selection; (iii) inducible factors, such as NF-AT and AP-1, that can be activated in mature (CD4+ CD8- TcRhigh) and immature (CD4- CD8- TcR-) thymocytes alike but not in the transitional stages when the cells (CD4+ CD8+ TcRlow) are subject to selection; and (iv) a factor containing CREB, which can be activated in thymocytes of all developmental stages by culture but does not require specific induction. These results verify that inducible transcription factors are targets of intrathymic developmental change. They also identify NF-AT and AP-1 as factors that are particularly sensitive to the mechanism altering thymocyte responses during the stages when thymocytes may undergo positive and negative selection.
Mol Cell Biol 1993 Jan
PMID:Molecular basis for developmental changes in interleukin-2 gene inducibility. 841 28

The nuclear signaling by the pleiotropic cytokine interleukin-6 (IL-6) has been investigated in human embryonal carcinoma cells and T cells. We show that Oct-1, a ubiquitously expressed octamer-binding protein known to be regulated posttranslationally, can also be regulated at the levels of mRNA and protein synthesis by IL-6 and by retinoic acid (RA) in human embryonal carcinoma cells. NF-IL6, an IL-6-inducible transcription factor of the C/EBP family, can confer this regulation and is itself regulated by both signals. The abundance and the molar ratios of the three forms of NF-IL6, corresponding to peptides initiated in frame from different AUGs of the same NF-IL6 mRNA species, are regulated by IL-6 and by RA. These results suggest that the two signal transduction pathways overlap in human embryonal carcinoma cells and that Oct-1 may be downstream of NF-IL6 in the shared regulatory cascade. Enhanced Oct-1 synthesis correlates with one of the functions of Oct-1, i.e., stimulation of adenovirus DNA replication. This provides an example of a possible functional consequence of IL-6 and RA signaling that is mediated by NF-IL6 and Oct-1 regulation.
Mol Cell Biol 1993 Apr
PMID:Convergent regulation of NF-IL6 and Oct-1 synthesis by interleukin-6 and retinoic acid signaling in embryonal carcinoma cells. 845 26

GHF-1 is a member of the POU family of homeodomain proteins. It is a cell-type-specific transcription factor responsible for determination and expansion of growth hormone (GH)- and prolactin-expressing cells in the anterior pituitary. It was previously suggested that cyclic AMP (cAMP)-responsive protein kinase A (PKA) phosphorylates GHF-1 at a site within the N-terminal arm of its homeodomain, thereby inhibiting its binding to the GH promoter. These results, however, are inconsistent with the physiological stimulation of GH production by the cAMP pathway. As reported here, cAMP agonists and PKA do not inhibit GHF-1 activity in living cells and although they stimulate the phosphorylation of GHF-1, the inhibitory phosphoacceptor site within the homeodomain is not affected. Instead, this site, Thr-220, is subject to M-phase-specific phosphorylation. As a result, GHF-1 DNA binding activity is transiently inhibited during the M phase. This activity is regained once cells enter G1, a phase during which GHF-1 phosphorylation is minimal. Thr-220 of GHF-1 is the homolog of the mitotic phosphoacceptor site responsible for the M-phase-specific inhibition of Oct-1 DNA binding Ser-382. As this site is conserved in all POU proteins, it appears that all members of this group are similarly regulated. A specific kinase activity distinct in its substrate specificity and susceptibility to inhibitors from the Cdc2 mitotic kinase or PKA was identified in extracts of mitotic cells. This novel activity could be involved in regulating the DNA binding activity of all POU proteins in a cell cycle-dependent manner.
Mol Cell Biol 1995 Dec
PMID:M-phase-specific phosphorylation of the POU transcription factor GHF-1 by a cell cycle-regulated protein kinase inhibits DNA binding. 852 34

The RNA polymerase II and III human small nuclear RNA promoters have a common basal element, the proximal sequence element, which binds the TATA box-binding protein-containing complex SNAPc. They also contain an enhancer characterized by a highly conserved octamer sequence, which constitutes a binding site for the broadly expressed POU domain transcription factor Oct-1. The POU domain is a bipartite DNA-binding domain consisting of a POU-homeo (POUH) domain and a POU-specific (POUs) domain joined by a flexible linker. Here, we show that the Oct-1 POU domain but not the related Pit-1 POU domain can facilitate the binding of SNAPc to the proximal sequence element, and activate transcription. The effect is probably mediated by protein-protein contacts, and 1 of 30 amino acid differences between the Oct-1 and Pit-1 POUs domains is the key determinant for the differential interaction with SNAPc and the ability to activate transcription. These results show that a function that is the hallmark of activation domains, namely, recruitment of a basal transcription complex resulting in activation of transcription, can be performed by a DNA-binding domain. In this case, subtle changes between activator DNA-binding domains, as subtle as a single amino acid difference, can profoundly affect interaction with the basal transcription machinery.
Mol Cell Biol 1996 May
PMID:The Oct-1 POU-specific domain can stimulate small nuclear RNA gene transcription by stabilizing the basal transcription complex SNAPc. 862 62

The rat CYP1A1 negative regulatory element (NRE) contains AP-1 and Oct-1 motifs at -808 to -788 bp. The CYP1A1 sequence from -813 to -779 bp and an identical sequence bearing a point mutation in the octamer motif were synthesized. Gel mobility shift assays showed the formation of two complexes with the wild-type CYP1A1 sequence and nuclear extracts from H4IIE and HepG2 hepatoma cells and from rat liver. The formation of the major complex was significantly reduced with the mutant octamer-containing oligomer and was specifically competed by an Oct-1 oligodeoxyribonucleotide. The addition of Oct-1 antibody caused a supershift of the major complex. The presence of the wild-type sequence, but not the mutant octamer sequence, caused a 3-fold decrease in SV40 enhancerless promoter activity in transfected HepG2 cells. Co-transfection of an Oct-1 expression vector with rat CYP1A1 NRE octamer-containing, promoter/reporter gene constructs specifically further decreased promoter activity of the wild-type octamer-containing constructs in HepG2 cells. The results indicate that Oct-1 binds to the rat CYP1A1 promoter NRE and is a negative regulator of rat CYP1A1 expression.
Mol Pharmacol 1996 Feb
PMID:Oct-1 transcription factor is a negative regulator of rat CYP1A1 expression via an octamer sequence in its negative regulatory element. 863 66

The human herpes simplex virus type 1 (HSV-1) transactivator VP16 and its homolog from bovine herpes-virus 1 (BHV-1) can each recruit the human homeodomain protein Oct-1 into a transcriptional regulatory complex. Here, we show that these two Oct-1 coregulators possess similar, if not identical, homeodomain recognition properties but possess different virus-specific cis-regulatory specificities: the HSV-1 VP-16 protein activates transcription from the HSV-1 VP16 response element, and the BHV-1 VP16 protein activates transcription from the BHV-1 VP16 response element. A distinct 3-bp segment, the D segment, lying 3' of the canonical TAATGARAT motif (where R is a purine) in the VP16 response element is responsible for the differential cis element recognition and transcriptional activation by these two homeodomain coregulators. These results demonstrate how a single homeodomain protein can direct differential transcriptional regulation by selective association with homologous homeodomain coregulators.
Mol Cell Biol 1996 Jun
PMID:Differential control of transcription by homologous homeodomain coregulators. 864 8

1. The packaging of nuclear DNA in chromatin determines the conversion of the genetic information into a defined phenotype by influencing the availability of DNA sequences for interactions with regulatory proteins and transcription factors. 2. We have studied the influence of the first level of chromatin organization, the nucleosome, on the activity of the mouse mammary tumor virus (MMTV) promoter. The MMTV promoter is strongly transcribed in response to steroid hormones but is virtually silent in the absence of hormonal stimuli. Full hormonal induction requires binding of the hormone receptors to four hormone-responsive elements (HREs), as well as binding of nuclear factor I (NFI) and the octamer transcription factor 1 (OTF-1 or Oct-1) to sites located between the HREs and the TATA box. A full loading with transcription factors cannot be achieved on free DNA due to steric hindrance between hormone receptor and NFI and between NFI and OTF-1. 3. The low basal activity of the MMTV promoter is most likely due to its organization in a positioned nucleosome. In the intact cell, as well in reconstituted chromatin, the regulatory region of the MMTV promoter is wrapped around a histone octamer in a precise rotational orientation, which permits access of the hormone receptors to only two of the four HREs, while precluding binding of NFI and OTF-1 to their respective sites. Upon hormone induction, the nucleosome is remodeled and the path of its DNA altered in a way which makes the nucleosomal dyad axis more accessible to DNase I and enables occupancy of all relevant sites: the four HREs, as well as the binding sites for NFI and OTF-1. 4. These results suggest that the nucleosomal organization of the MMTV promoter not only is responsible for the low activity prior to hormone treatment, but also may be a prerequisite for full loading with transcription factors after hormone induction. We conclude that the DNA contains topological information which modulates the expression of the genetic program.
Cell Mol Neurobiol 1996 Apr
PMID:Chromatin structure of the MMTV promoter and its changes during hormonal induction. 874 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>