Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q02556 (DNA-binding domain)
 6,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wilms tumor is a pediatric kidney cancer that has been linked to the inactivation of a tumor-suppressor gene at chromosome locus 11p13. The WT1 gene, mapping to this locus, is developmentally regulated in the kidney and encodes a putative transcription factor that has been shown to be mutated in Wilms tumor specimens. We have suggested that one such altered product of the WT1 gene may be capable of trans-dominant suppression, since the mutated allele was found to be coexpressed with the wild-type allele in a sporadic Wilms tumor. We therefore tested the ability of this mutant WT1 allele, containing an in-frame deletion within the DNA-binding domain, to transform primary baby rat kidney cells. The mutant WT1 gene was found to cooperate with the adenoviral E1A gene in transforming baby rat kidney cells, as demonstrated by growth in soft agar and tumorigenicity in nude mice. The wild-type WT1 gene in all of its alternatively spliced forms neither suppressed E1A-induced focus formation nor cooperated with E1A. Our results indicate that impairment of DNA binding of the WT1 tumor-suppressor gene product can result in a dominant negative mutation.
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PMID:A dominant mutation in the Wilms tumor gene WT1 cooperates with the viral oncogene E1A in transformation of primary kidney cells. 132 31

We have isolated a putative transcription factor gene, PosF21, from Arabidopsis thaliana using an indirect cross-hybridization approach. cDNA clones were isolated which encode single repeating amino acids. Such sequences may function as activation domains in transcription factors and may be indicative for such proteins. The clone PosF21 encodes a region very rich in glutamines. Besides this putative activation domain it encodes a protein sequence which shows all the characteristics of a basic-domain/leucine zipper type of DNA-binding domain. PosF21 is expressed constitutively at a low level in young seedlings and in roots, stems and leaves of mature Arabidopsis plants. A genomic clone of PosF21 was isolated and the gene structure was analyzed. Related sequences in Arabidopsis and a wide range of other plants were detected using the putative DNA-binding domain as a probe in cross-hybridization experiments. Transient transformations in tobacco protoplasts were performed using the beta-glucuronidase (GUS) gene as reporter gene. Approximately 400 bp of the 5' genomic region of PosF21 promote expression of the GUS gene in tobacco protoplasts. Evidence for a regulatory function of PosF21 was obtained since co-expression of the full PosF21 protein or its DNA-binding region alone specifically stimulated GUS gene expression directed from the PosF21 promoter by 6-8-fold.
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PMID:Isolation and molecular characterization of PosF21, an Arabidopsis thaliana gene which shows characteristics of a b-Zip class transcription factor. 184 85

To identify genes that can repress the expression of growth regulatory molecules, a human fetal cDNA library was screened with a degenerate oligonucleotide that corresponds to the conserved stretch of 6 amino acids connecting successive zinc-finger regions in the Wilms' tumor suppressor/Egr-1 family of DNA-binding proteins. One clone, designated zinc-finger protein 174 (ZNF174), corresponds to a putative transcription factor with three zinc fingers and a novel finger-associated domain, designated the SCAN box. The three Cys2-His2-type zinc fingers are positioned at the carboxyl terminus, while the 65-amino acid finger-associated SCAN box is located near the amino terminus. Chromosomal localization using somatic cell hybrid analysis and fluorescent in situ hybridization mapped the gene for ZNF174 to human chromosome 16p13.3. The 2.5-kilobase transcript from this gene is expressed in a variety of human organs, but most strongly in adult testis and ovary. Fusion of the upstream regulatory region of ZNF174 to the DNA-binding domain of GAL4 revealed that the gene could confer a repression function on the heterologous DNA-binding domain. ZNF174 selectively repressed reporter activity driven by the platelet-derived growth factor-B chain and transforming growth factor-beta 1 promoters and bound to DNA in a specific manner. This member of the C2H2-type zinc-finger family is a novel transcriptional repressor.
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PMID:Isolation and characterization of a novel zinc-finger protein with transcription repressor activity. 767 92

Using polymerase chain reaction and two degenerate primers whose designs were based on the two best conserved regions of the DNA-binding domain of the nuclear receptor superfamily, we identified and cloned a novel orphan receptor, named TAK1. The open reading frame of TAK1 encodes a protein of 596 amino acid residues. Based on the modular structure and the presence of a DNA-binding domain containing two zinc fingers TAK1 belongs to the steroid/thyroid hormone receptor superfamily. The amino acid sequence of TAK1 is most closely related to the orphan receptor TR2-11. Their overall sequence homology is 64%, with the highest similarity (82%) being observed in the DNA-binding domain. Northern blot analysis using RNA from multiple human tissues showed that a 9.4 kilobase TAK1 transcript was expressed ubiquitously and that the presence of a 2.8 kilobase mRNA was largely restricted to the testis. In situ hybridization using sections of rat and mouse testes and Northern blot analysis using RNA from testes of rats at various ages revealed that TAK1 is most abundantly expressed in spermatocytes whereas little expression was observed in other germ cells or somatic cells. In situ hybridization using other mouse and rat tissues revealed cell type-specific expression of TAK1 in several tissues. Our observations suggest a role for this putative transcription factor in the regulation of gene expression in specific cell types. In the testis, TAK1 appears to control gene expression during spermatogenesis, particularly during the meiotic phase.
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PMID:TAK1: molecular cloning and characterization of a new member of the nuclear receptor superfamily. 770 55

We have identified and cloned a novel member of the nuclear receptor superfamily from murine testis, referred to as retinoid receptor-related testis-associated receptor or RTR. Degenerate PCR primers homologous to two conserved regions of the DNA-binding domain of members of this superfamily were employed to identify this gene. The amino-acid sequence of RTR is most closely related to that of the mouse RXRs with an overall identity of 32-34%; the highest similarity (61%) is observed in the DNA-binding domain. Northern blot analysis using RNA from multiple tissues showed that RTR is predominantly expressed in the testis. Northern blot analysis using RNA from different testicular cell types showed that RTR mRNA is not expressed in early germ cells or Sertoli cells but is most abundant in round spermatids. Our observations suggest that this putative transcription factor plays a role in the regulation of gene expression particularly during the post-meiotic phase of spermatogenesis.
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PMID:RTR: a new member of the nuclear receptor superfamily that is highly expressed in murine testis. 783 9

Translocations involving chromosome band 11q23, found in acute lymphoid and myeloid leukemias, disrupt the MLL gene. This gene encodes a putative transcription factor with homology to the zinc fingers and other domains of the Drosophila trithorax gene product and to the "AT-hook" motif of high mobility group proteins. To map potential transcriptional activation or repression domains of the MLL protein, yeast GAL4 DNA-binding domain and MLL hybrid protein-expressing plasmids were cotransfected with chloramphenicol acetyltransferase reporter plasmids in a transient transfection system. We found that MLL contains a strong activation domain and a repression domain. The former, located telomeric (3') to the breakpoint region, activated transcription 18-fold to > 200-fold, depending on the promoter and cell line used for transfection. A repression domain that repressed transcription 4-fold was located centromeric (5') to the breakpoint region of MLL. The MLL AT-hook domain protein was expressed in bacteria and was utilized in a gel mobility shift assay to assess DNA-binding activity. The MLL AT-hook domain could bind cruciform DNA, recognizing structure rather than sequence of the target DNA. In translocations involving MLL, loss of an activation domain with retention of a repression domain and a DNA-binding domain on the der(11) chromosome could alter the expression of downstream target genes, suggesting a potential mechanism of action for MLL in leukemia.
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PMID:11q23 translocations split the "AT-hook" cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene. 793

SRY, a putative transcription factor encoded by the sex-determining region of the human Y chromosome, regulates a genetic switch in male development. Impairment of this switch leads to intersex abnormalities of the newborn and is observed in association with mutations in the SRY DNA-binding domain [the high-mobility-group (HMG) box]. Here we show that the SRY HMG box exhibits a novel mechanism of DNA recognition: partial intercalation of a nonpolar side chain in the DNA minor groove. Base stacking (but not base pairing) is interrupted at the site of insertion. Sequence specificity reflects topological requirements of partial intercalation rather than direct readout of base-specific functional groups. Our results predict that the SRY HMG box inserts an alpha-helix into a widened minor groove at the center of a sharp DNA bend. A similar mechanism may underlie binding of SRY and homologous HMG proteins to four-way junctions (Holliday intermediates) and other noncanonical DNA structures.
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PMID:The SRY high-mobility-group box recognizes DNA by partial intercalation in the minor groove: a topological mechanism of sequence specificity. 826 59

We describe the isolation of human LH-2, a putative transcription factor containing two cysteine-rich regions (LIM domains) and a homeobox (Hox) DNA-binding domain. High levels of hLH-2 expression were observed in all cases of chronic myelogenous leukaemia (CML) tested, regardless of disease status. hLH-2 was mapped to chromosome 9Q33-34.1, in the same region as the reciprocal translocation that creates the BCR-ABL chimera of the Philadelphia chromosome (Ph'), the hallmark of CML; hLH-2 was retained on the derivative 9 chromosome and is therefore centromeric of c-ABL. The proximity of hLH-2 to the breakpoint on chromosome 9 raises the possibility of cis-activation by the t(9;22)(q34;q11) translocation. In addition to finding hLH-2 expression in all cases of CML, expression was observed in lymphoid malignancies and myeloid cell lines, but not in primary cases of acute myelogenous leukaemia. The role of hLH-2 in the development or progression of leukaemia is not known. However, hLH-2 may prove useful as a marker of CML for monitoring residual disease.
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PMID:Identification of a human LIM-Hox gene, hLH-2, aberrantly expressed in chronic myelogenous leukaemia and located on 9q33-34.1. 864 22

The wheat bZIP protein HBP-1a(17) is a putative transcription factor regulating histone gene expression. To delineate the functional domain(s) of this factor, we made a series of effector constructs expressing fusion proteins, in which various portions of HBP-1a(17) are fused to the DNA-binding domain of the yeast transcriptional activator GAL4, in plant cells. When the beta-glucuronidase (GUS) reporter gene, driven by the wheat histone H3 core promoter harboring the GAL4-binding sequence, was co-transfected with such effector genes into tobacco protoplasts, several portions of HBP-1a(17) influenced reporter gene expression. The N-terminal one-third of HBP-1a(17), termed the P region (residues 1-118) due to its Pro content, did not activate the reporter gene, in contrast to the corresponding Pro-rich region of Arabidopsis GBF1 (residues 1-110), which functions as an activation domain. When the P region was divided into two, however, both its N-terminal (1-56; termed NP) and C-terminal (58-118; termed PC) halves were able to enhance expression of the reporter gene. When the NP region was further divided into NP(5-30) and NP(30-56), both regions still retained activating ability. These results suggest that the P region of HBP-1a(17) is composed of several modules each having activating function, and modification and/or conformational changes of the P region might influence its function.
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PMID:Dissection of the wheat transcription factor HBP-1a(17) reveals a modular structure for the activation domain. 906 88

We have identified a putative transcription factor, designated hLim-1, from human fetal brain using degenerate polymerase chain reaction (PCR) and cDNA library screening. The deduced open reading frame, derived from sequencing a 3.0-kb hLim-1 cDNA, encodes a protein of 384 amino acids with two cysteine-rich LIM domains and one homeobox (HOX) DNA-binding domain. The nucleotide sequence of hLim-1 cDNA is 87% identical to mouse Lim-1 and the predicted amino acid sequence is greater than 97% conserved. Expression patterns of hLim-1 were evaluated by Northern analysis and reverse transcription (RT)-PCR coupled with Southern blotting. HLim-1 expression was observed in human brain, thymus, and tonsillar tissue. Expression of hLim-1 was also observed in 58% of acute myelogenous leukemia (AML) cell lines and in four of five primary samples from patients with chronic myeloid leukemia (CML) in myeloid blast transformation. The gene encoding hLim-1 was mapped using fluorescence in situ hybridization (FISH) to human chromosome 11p12-13. The expression pattern and structural characteristics of the hLim-1 gene suggest that it encodes a transcriptional regulatory protein involved in the control of differentiation and development of neural and lymphoid cells. Its expression in CML in blast crisis suggests that it may be involved with progression in this disease; a prospective study is required to confirm this.
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PMID:Cloning, expression, and chromosomal localization to 11p12-13 of a human LIM/HOMEOBOX gene, hLim-1. 921 61


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