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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The apparent preferential expression of the elastase/cathepsin G protease inhibitor antileukoproteinase (ALP) in endometrium of species with epitheliochorial placenta suggests mechanisms of transcriptional regulation unique to these mammalian species. To begin to define the cis-acting regulatory elements involved in the endometrial transcription of the ALP gene, the porcine ALP gene was isolated and characterized. The porcine gene spans at least 13 kb and consists of 5 exons and 4 introns. This genomic structure, except for an additional exon, is similar to that of the human gene where the first three exons encode the signal peptide, trypsin/cathepsin G binding region, and elastase binding region, respectively. The positions of the 16 cysteine residues in exons 2 and 3 of the human gene are conserved in the porcine gene. The porcine gene contains a TATA box at -29 nucleotide (nt), and sequences with limited homology to those which might bind the transcription factors AP-1, AP-2, Sp-1 and Oct-1. The functional promoter activity of the ALP-5' flanking DNA was examined using chimeric ALP-chloramphenicol acetyl transferase (CAT) DNA constructs, after transient transfection in human (ECC-1, Ishikawa) and rabbit (HRE-H9) endometrial and human trophoblastic (JEG-3) cell lines. A 887 nt fragment of the ALP-5'-flanking region (-887ALP-pCAT-E) was active in these cell lines, with the highest promoter activity observed in the ECC-1. Progressive 5' deletion of the 887 nt fragment up to -243 nt had no effect on CAT gene expression in all cell lines, relative to the longest construct.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1993 Nov
PMID:Chromosomal organization of the gene encoding porcine antileukoproteinase and functional analysis of the promoter region in endometrial and placental cells. 790 70

POU domain proteins have been implicated as regulators of differentiation and development, particularly in early embryogenesis and in neural morphogenesis. Given that neural and epidermal lineages originate from a common precursor (ectodermal) cell, we explored the possibility that POU proteins are involved in epidermal differentiation. Using reverse transcription-PCR and degenerate oligonucleotides, we generated several POU domain cDNAs from cultured human epidermal mRNAs. One of these encoded a sequence identical to the rodent Tst-1/SCIP/Oct-6 POU domain. Subsequently, we isolated a cDNA encoding a 45.3-kDa protein with 98% sequence identity to rat Tst-1/SCIP and 94% identity to mouse Oct-6. This protein bound specifically to the canonical octamer motif, warranting its designation as human Oct-6. By RNase protection assays, by PCR, and by immunoblot analysis, Oct-6 was expressed in cultured epidermal keratinocytes. By in situ hybridization, Oct-6 mRNA was detected not only in epidermis but also a variety of other stratified squamous epithelia and with greater signals than testis, the tissue in which this POU protein was originally discovered. Moreover, Oct-6 exerted a marked and specific negative influence on expression of the K5 and K14 genes, abundantly expressed in most dividing stratified squamous epithelial cells and downregulated as cells commit to terminally differentiate. The repressive effect was complex, but it was not observed with Oct-1, nor was it seen with a truncated Oct-6 missing the POU domain. Taken together, our studies suggest that Oct-6 may play an important role in controlling gene expression in stratified squamous epithelia, including epidermis.
Mol Cell Biol 1994 May
PMID:Oct-6: a regulator of keratinocyte gene expression in stratified squamous epithelia. 790 56

Understanding how diverse transcription patterns are achieved through common factor binding elements is a fundamental question that underlies much of developmental and cellular biology. One example is provided by the fibroblast growth factor 4 (FGF-4) gene, whose expression is restricted to specific embryonic tissues during development and to undifferentiated embryonal carcinoma cells in tissue culture. Analysis of the cis- and trans-acting elements required for the activity of the previously identified FGF-4 enhancer in F9 embryonal carcinoma cells showed that enhancer function depends on sequences that bind Sp1 and ubiquitous as well as F9-specific octamer-binding proteins. However, sequences immediately upstream of the octamer motif, which conform to a binding site for the high-mobility group (HMG) domain factor family, were also critical to enhancer function. We have identified a novel F9-specific factor, Fx, which specifically recognizes this motif. Fx formed complexes with either Oct-1 or Oct-3 in a template-dependent manner. The ability of different enhancer variants to form the Oct-Fx complexes correlated with enhancer activity, indicating that these complexes play an essential role in transcriptional activation of the FGF-4 gene. Thus, while FGF-4 enhancer function is octamer site dependent, its developmentally restricted activity is determined by the interaction of octamer-binding proteins with the tissue-specific factor Fx.
Mol Cell Biol 1994 Dec
PMID:Interaction between a novel F9-specific factor and octamer-binding proteins is required for cell-type-restricted activity of the fibroblast growth factor 4 enhancer. 796 17

Earlier, a number of DNA fragments were identified in the complex form of DNA polymerase alpha. One of them, DARC146, can support autonomous replication in mammalian cells. We have subcloned 146 bp from DARC146 (here called DARC146). This fragment has an ability to replicate autonomously in mammalian cells. This ability permits one to speak about DARC146 as a putative replication origin. From this conclusion, we suggest that all signals for initiation of DNA synthesis are located on the nucleotide sequence under study. Here, we have shown that the nuclear extract contains four polypeptides binding specifically to synthetic oligonucleotides covering the AT-rich region of the DARC146 sequence. The first protein is Oct-1, a nuclear transcription-replication factor. The second protein (named p65) binds to the TCTCTTA site of the DARC146 nucleotide sequence. There are two sites for Oct-1 protein and two sites for p65 in the DARC146 fragment. Octamer motifs and sites for p65 are located tandemly side by side. Moreover, we identified 28kDa polypeptide from nuclear matrix which bound to DARC146. Based upon the data presented, we suggest a hypothetical model of the pre-initiation state of the DARC146 sequence.
Mol Biol (Mosk)
PMID:[DNA fragment DARC146 from a complex form of DNA polymerase alpha contains several nuclear protein binding segments]. 799 Aug 10

Comparison analysis was made of the putative replication origin DARC146 and the origin determined in the DNFR domain of CHO cells. We failed to observe extensive homology between these two sequences. However, several short (8-10 bp) areas of homology were identified. Some of them are binding sites for nuclear proteins. As shown by GM and competition experiments, both origins contain high-affinity binding sites for the transcription-replication factor Oct-1 and for two unknown nuclear factors. The two unknown nuclear factors bound to TCTCTTA and CACTTAG nucleotides. The binding sites for these proteins are located at a short distance from each other. This fact suggests interaction between these polypeptides. Measurement of DNA-binding activity of Oct-1 during the cell cycle of proliferating hepatocyte demonstrated that the binding activity of Oct-1 protein increased before initiation of DNA synthesis. The results of this report suggest that Oct-1 and two other nuclear proteins participate in the regulation of mammalian DNA replication. The results published early indicated the presence of an unusual DNA structure (bent DNA) in both origins under study. We suggest that these common elements of the origins regulate their activation.
Mol Biol (Mosk)
PMID:[Segments initiating replication of the dihydrofolate reductase domain and the DNA fragment DARC146 interact with the same nuclear proteins]. 799 Aug 15

The B-cell POU homeodomain protein Oct-2 contains two transcriptional activation domains, one N terminal and the other C terminal of the central DNA-binding POU domain. The synergistic action of these two activation domains makes Oct-2 a more potent activator of mRNA promoters than the related broadly expressed octamer motif-binding protein Oct-1, which contains an N-terminal but not a C-terminal Oct-2-like activation domain. Both Oct-2 mRNA promoter activation domains were delineated by truncation analysis: the N-terminal Q domain is a 66-amino-acid region rich in glutamines, and the C-terminal P domain is a 42-amino-acid region rich in prolines. The Q and P domains synergized with each other or duplicates of themselves, independently of their N-terminal or C-terminal position relative to the POU domain. The C-terminal P domain, which differentiates Oct-2 from Oct-1, also activated transcription in conjunction with the heterologous GAL4 DNA-binding domain. Oct-2 thus contains three modular functional units, the DNA-binding POU domain and the two P and Q activation domains. An electrophoretic mobility shift assay with a variety of these Oct-2 activators revealed a distinct complex called QA that was dependent on the presence of an active glutamine-rich activation domain and migrated more slowly than the Oct-2-DNA complexes. Formation of the QA complex is consistent with interaction of the glutamine-rich activation domains with a regulatory protein important for the process of transcriptional activation.
Mol Cell Biol 1994 Sep
PMID:The Oct-2 glutamine-rich and proline-rich activation domains can synergize with each other or duplicates of themselves to activate transcription. 806 38

POU domain proteins have been implicated in the regulation of a number of lineage-specific genes. Among the first POU domain proteins described were the immunoglobulin octamer-binding proteins Oct-1 and Oct-2. It was therefore of special interest when we identified a novel lymphoid POU domain protein in Southwestern (DNA-protein) screens of T-cell lambda gt11 libraries. This novel POU protein, TCF beta 1, binds in a sequence-specific manner to a critical motif in the T-cell receptor (TCR) beta enhancer. Sequence analysis revealed that TCF beta 1 represents a new class of POU domain proteins which are distantly related to other POU proteins. TCF beta 1 is encoded by multiple exons whose organization is distinct from that of other POU domain proteins. The expression of TCF beta 1 in a tissue-restricted manner and its ability to bind to multiple motifs in the TCR beta enhancer support a role in regulating TCR beta gene expression. The expression of TCF beta 1 in both B and T cells and the ability of recombinant TCF beta 1 to bind octamer and octamer-related motifs suggest that TCF beta 1 has additional roles in lymphoid cell function. The ability of TCF beta 1 to transactivate in a sequence-specific manner is consistent with a role for regulating lymphoid gene expression.
Mol Cell Biol 1993 Sep
PMID:A novel POU domain protein which binds to the T-cell receptor beta enhancer. 810 89

Pit-1, a member of the POU family of homeo-domain transcription factors, activates prolactin and GH gene expression but also has a role in pituitary cell differentiation and proliferation. Expression of Pit-1 may therefore be of central importance in the function and phenotype of human pituitary adenomas. We have found evidence that, in addition to Pit-1 mRNA, Pit-1-like immunoreactivity and DNA-binding activity are readily detectable in a series of human pituitary adenomas. Gel mobility shift assays using adenoma protein extracts with two Pit-1-binding sites from the human prolactin gene promoter demonstrated the formation of several DNA sequence-specific protein-DNA complexes; some of these could be accounted for by Oct-1-binding activity. Pit-1 activity was anticipated in prolactin- and GH-secreting adenomas, but was also detected in a proportion of endocrine-inactive (non-secreting) adenomas that did not express Pit-1 target genes. The data demonstrate the presence of Pit-1 in a range of pituitary adenomas. Different adenomas generated slightly differing patterns of DNA-binding activity, though Pit-1 mRNA and protein size appeared normal in all tumours so far examined.
J Mol Endocrinol 1993 Dec
PMID:Expression of Pit-1 and related proteins in diverse human pituitary adenomas. 814 36

VP16 is a herpes simplex virus (HSV)-encoded transcriptional activator protein that is essential for efficient viral replication and as such may be a target for novel therapeutic agents directed against viral gene expression. We have reconstituted transcriptional activation by VP16 in an in vitro system that is dependent on DNA sequences from HSV immediate-early gene promoters and on protein-protein interactions between VP16 and Oct-1 that are required for VP16 activation in vivo. Activation increased synergistically with the number of TAATGARAT elements (the cis-acting element for VP16 activation in vivo) upstream of the core promoter, and mutations of this element that reduce Oct-1 or VP16 DNA binding reduced transactivation in vitro. A VP16 insertion mutant unable to interact with Oct-1 was inactive, but, surprisingly, a deletion mutant lacking the activation domain was approximately 65% as active as the full-length protein. The activation domains of Oct-1 were necessary for activation in reactions containing the VP16 deletion mutant, and they contributed significantly to activation by full-length VP16. Addition of a GA-rich element present in many HSV immediate-early gene enhancers synergistically stimulated VP16-activated transcription. Finally, oligopeptides that are derived from a region of VP16 thought to contact a cellular factor known as HCF (host cell factor) and that inhibit efficient VP16 binding to the TAATGARAT element also specifically inhibited VP16-activated, but not basal, transcription. Amino acid substitutions in one of these peptides identified three residues that are absolutely required for inhibition and presumably for interaction of VP16 with HCF.
Mol Cell Biol 1994 May
PMID:Transcriptional activation by herpes simplex virus type 1 VP16 in vitro and its inhibition by oligopeptides. 816 93

The hepatitis B virus 17 kDa x gene product expressed in bacteria transactivates a human U6 promoter three- to eightfold in an ATP-independent manner in HeLa cell NTP-depleted extracts containing preassembled transcription preinitiation complexes. However, if added prior to assembly, HBx squelches the promoter. Both the HBx dependent "squelching" of U6 transcription observed in transient transfection analysis, and the transactivation observed in vitro is dependent on the presence of an upstream octamer element. HBx is incorporated via protein-protein interactions into DNA complexes containing the activation domains of Oct-1, and into a stable U6 preinitiation complex. This is consistent with a role as a coactivator interacting with the basal transcription machinery. We propose that the HBx dependent transactivation and repression of U6 transcription occurs by changes in the transcription factor limiting initiation, and propose that HBx may have a dual role in the regulation of transcription in vivo.
Cell Mol Biol Res 1993
PMID:The 17 kDa HBx protein encoded by hepatitis B virus interacts with the activation domains of Oct-1, and functions as a coactivator in the activation and repression of a human U6 promoter. 817 91


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