Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “gene function”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,675 records · Page 93Linked to original sources
PubMed1987

The phoBR operon in Escherichia coli K-12.

The phoB and phoR genes encode a transcription activator and a sensory protein of the phosphate regulon, respectively. It is shown here that they were transcribed as an operon in which the phoB gene was promoter proximal. Although an operon structure was suggested previously (K. Makino, H. Shinagawa, M. Amemura, and A. Nakata, J. Mol. Biol. 190:37-44 and 192:549-556, 1986), previous results showed only that phoR gene expression during phosphate limitation is dependent on the upstream phoB promoter. The phoR gene could still have had its own promoter for expression in the presence of phosphate. Two polar transposon-induced mutations are described which simultaneously abolished phoB and phoR gene function in cis; one mutation mapped in the phoB gene, and the other mapped upstream of the phoB gene. These results demonstrate an operon structure, in which phoR gene function required expression from the phoB promoter. Unexpectedly, an antisense pho omega Mu d1(lacZ) insertion within the promoter-proximal end of the phoB gene expressed the lacZ reporter gene, thus allowing for the possibility that the phoBR operon is regulated by an antisense RNA.

Bacterial Proteins↗
PubMed2006

[The mouse hairless gene: its function in hair root and at the heart of a subtle pleiotropy].

The hairless gene in mammals encodes a nuclear factor that is highly expressed in skin and appears to control hair follicle integrity and cycling. In the absence of a normal and functional Hairless (Hr) protein, the hair bulb undergoes premature apoptosis during the first catagen stage of the hair cycle. The most striking effects of the mutation are loss of hair follicles and formation of epidermal utricles and dermal cysts. The hairless gene expression appears to be widespread and temporally regulated. The gene is strongly expressed in different compartments of the brain. Hairless mRNAs were detected in cartilage, gonads, thymus and colon. In addition to alopecia, hairless mice strains show subtle defects in the development and differentiation of various tissues and organs. The Hr protein is localised in cell nuclei and functions as a transcriptional regulator. Although its role has not been resolved in molecular terms, it was demonstrated that Hr is able to interact with multiple nuclear hormone receptors. Hr seems to be a part of a large multiprotein complex capable to repress transcription by its association to chromatin remodelling factors such as histone deacetylases. Recent experimental data suggest that Hr might be involved in Hox gene regulation, cell adhesion modulation and progenitor cells identity. At least in the skin, but probably in other organs, the Hr repressor seems to be responsible for the timing of epithelial cells differentiation.

Alopecia↗
PubMed1989

Conservation of polyhedrin gene promoter function between Autographa californica and Mamestra brassicae nuclear polyhedrosis viruses.

The DNA sequence of the polyhedrin gene of the Mamestra brassicae multiple nucleocapsid nuclear polyhedrosis virus (MbMNPV) was determined and compared with the polyhedrin genes of Autographa californica (Ac) and Panolis flammea (Pf) MNPVs. Using this information, a transfer vector was constructed based on the EcoRI I fragment of AcMNPV in which the polyhedrin promoter was replaced by the homologous region extending 481 nucleotides upstream from the MbMNPV polyhedrin coding sequence. The Escherichia coli lacZ gene was also included downstream from the putative MbMNPV promoter. Cotransfection of this transfer vector with wild-type AcMNPV DNA produced stable recombinant viruses expressing the lacZ gene under the control of the MbMNPV polyhedrin promoter. The levels of beta-galactosidase produced by these recombinants in infected cells were 30% lower than the expression level obtained from viruses with the authentic AcMNPV promoter in front of the lacZ gene. The MbMNPV promoter has thus been shown to function efficiently in the genetic environment of AcMNPV. The implications of this finding for the release of genetically manipulated baculovirus insecticides and for the construction of baculovirus multiple expression vectors are discussed.

Amino Acid Sequence↗
PubMedDate not supplied

Evidence that the recently discovered theta 1-globin gene is functional in higher primates.

A new subfamily of the alpha-globin-like family has recently been identified in higher primates, rabbit, galago and possibly the horse. One member of this subfamily, theta 1, is downstream from the adult alpha 1-globin gene. In orang-utan, but not in rabbit or galago, the theta 1-gene appears to be structurally intact, suggesting that it may be functional in this species. The orang-utan theta 1-gene possesses initiation and termination codons, and the predicted polypeptide differs from the orang-utan alpha 1-globin by 55 amino acids. The upstream promoter boxes CCAAT and ATA are present, although approximately 150 base pairs (bp) farther upstream than in the alpha 1-gene. This structural difference in the promoter between the orang-utan theta 1- and alpha 1-genes has led Proudfoot to speculate that the theta 1-gene may be inactive. We have now cloned the theta 1- and alpha 1-globin genes from the olive baboon, and have compared their sequences with those of orang-utan. The unique promoter structure of the orang-utan theta 1-gene is highly conserved in baboon, although the orang-utan and baboon diverged nearly 30 million years ago. The coding sequences of the two theta 1-genes differ by only 6.3% with 22 out of 27 nucleotide substitutions being codon third position silent changes. These data support the view that the theta 1-gene has been functional in the baboon, orang-utan, and by implication, in man. We also estimate that the duplication event generating the theta 1- and alpha-globin-like subfamilies may have occurred as much as 260 million years ago.

Amino Acid Sequence↗
PubMed1999

Formin defines a large family of morphoregulatory genes and functions in establishment of the polarising region.

Formin was originally isolated as the gene affected by the murine limb deformity (ld) mutations, which disrupt the epithelial-mesenchymal interactions regulating patterning of the vertebrate limb autopod. More recently, a rapidly growing number of genes with similarity to formin have been isolated from many different species including fungi and plants. Genetic and biochemical analysis shows that formin family members function in cellular processes regulating either cytokinesis and/or cell polarisation. Another common feature among formin family members is their requirement in morphogenetic processes such as budding and conjugation of yeast, establishment of Drosophila oocyte polarity and vertebrate limb pattern formation. Vertebrate formins are predominantly nuclear proteins which control polarising activity in limb buds through establishment of the SHH/FGF-4 feedback loop. Formin acts in the limb bud mesenchyme to induce apical ectodermal ridge (AER) differentiation and FGF-4 expression in the posterior AER compartment. Finally, disruption of the epithelial-mesenchymal interactions controlling induction of metanephric kidneys in ld mutant embryos indicates that formin might function more generally in transduction of morphogenetic signals during embryonic pattern formation.

Amino Acid Sequence↗
PubMed1983

Isolation and transcriptional characterization of three genes which function at start, the controlling event of the Saccharomyces cerevisiae cell division cycle: CDC36, CDC37, and CDC39.

The genes CDC36, CDC37, and CDC39, thought to function in the cell division control process in Saccharomyces cerevisiae, were isolated from a recombinant plasmid library prepared by partial digestion of S. cerevisiae genomic DNA with Sau3A and insertion into the S. cerevisiae-Escherichia coli shuttle vector YRp7. In each case, S. cerevisiae DNA sequences were identified which could complement mutant alleles of the gene in question and which could direct integration of a plasmid at the chromosomal location known to correspond to that gene. Complementing DNA segments were subcloned to remove extraneous coding regions. The coding regions corresponding to CDC36, CDC37, and CDC39 were then identified and localized by R-loop analysis. The estimated sizes of the three coding regions were 615, 1,400, and 2,700 base pairs, respectively. Transcriptional orientation of the coding regions was established by using M13 vectors to prepare strand-specific probes followed by hybridization to blots of electrophoresed S. cerevisiae mRNA. The intracellular steady-state abundance of the mRNA species corresponding to the genes was estimated by comparing hybridization signals on RNA blots to that of a previously determined standard, the cell cycle start gene CDC28. The quantities calculated for the three mRNA species were low, ranging from 1.5 +/- 1 copies per haploid cell for the CDC36 mRNA to 3.1 +/- 1.5 and 4.6 +/- 2 copies per haploid cell for the CDC37 and CDC39 mRNAs, respectively. The CDC28 mRNA had been previously estimated at 7.0 +/- 2 copies per cell.

Cell Cycle↗
PubMed2003

Gene therapy of gliomas.

Malignant glioma formation is associated with characteristic genetic alterations, although epigenetic mechanisms may contribute in tumorigenesis. Until recently, our knowledge has mainly been based on chromosomal and molecular studies performed in the last two decades. This has increased tremendously with the advent of new technologies, in particular expression arrays for simultaneous analysis of thousands of genes. Consequently, gene therapy of gliomas may aim at molecular interference with 'gain of function' genes (oncogenes) or replacement of 'loss of function' genes (tumor suppressor genes). Such approaches require transgene expression in whole tumor cell populations (if not other mechanisms come into play) which cannot be achieved with current vector systems. Hence other strategies have been pursued which may be independent of genes actually involved in tumorigenesis. Microbial genes (e.g. herpes simplex virus thymidine kinase) may be transferred into the tumors allowing for prodrug activation (e.g. ganciclovir). Furthermore, cytokines or other immunomodulatory genes may be used for vaccination purposes which frequently involves ex vivo transfection of autologous tumor cells with such genes. These approaches proved promising in preclinical studies performed in cell culture and different inbred rodent models. A considerable number of clinical trials have been initiated based on these approaches. Although most therapeutic strategies proved safe, clinical responses fell short of expectations raised by preclinical results. This, to a large extent, has to be attributed to a lag in the development of efficient vector systems. Although much effort has been put into this area of research, neuro-oncologists are still in await of a vector system allowing for selective and efficient tumor cell transduction. This has led to increased interest in distinct but related strategies, e.g. oncolytic viruses or direct intra-tumoral delivery of anti-sense oligonucleotides.

Animals↗
PubMed2003

Structure of the murine tenascin-R gene and functional characterisation of the promoter.

The tenascin-R (TN-R) gene encodes a multidomain extracellular matrix glycoprotein belonging to the tenascin family. It is detectable mainly in oligodendrocytes and neuronal subpopulations of the central nervous system. In this report, we describe the structure of the 5'-region of the mouse TN-R gene and characterise the activity of its promoter. By in silico cloning and genome walking, we have deduced the organisation of the gene and identified the promoter sequence by 5'-RACE technology. TN-R transcripts in adult mouse brain contain non-coding exons 1 and 2 as demonstrated by the reverse transcriptase-polymerase chain reaction. The promoter displays its activity in cultured cells of neural origin, but not in a fibroblast-like cell line or an undifferentiated teratocarcimoma cell line. As for the human and rat genes, the elements required for the full and cell type-specific activity of the promoter are contained in exon 1 and 167 bp upstream of this exon. The mouse TN-R promoter sequence is similar to that of rat and human in that it displays similarly unusual features: it lacks any classical TATA-box or CAAT-box, GC-rich regions or initiator elements. The promoter contains consensus sequences for binding of a variety of transcription factors, notably p53/p73 and glucocorticoid receptors.

Animals↗
PubMed2006

The relationship between protein sequences and their gene ontology functions.

BACKGROUND: One main research challenge in the post-genomic era is to understand the relationship between protein sequences and their biological functions. In recent years, several automated annotation systems have been developed for the functional assignment of uncharacterized proteins. The underlying assumption of these systems is that similar sequences imply similar biological functions. However, it has been noted that matching sequences do not always infer similar functions. RESULTS: In this paper, we present the correlation between protein sequences and protein functions for the yeast proteome in the context of gene ontology. A novel measure is introduced to define the overall similarity between two protein sequences. The effects of the level as well as the size of a gene ontology group on the degree of similarity were studied. The similarity distributions at different levels of gene ontology trees are presented. To evaluate the theoretical prediction power of similar sequences, we computed the posterior probability of correct predictions. CONCLUSION: The results indicate that protein pairs of similar biological functions tend to have higher sequence similarity, although the similarity distribution in each functional group is heterogeneous and varies from group to group. We conclude that sequence similarity can serve as a key measure in protein function prediction. However, the resulting annotations must be verified through other means. A method that combines a broader range of measures is more likely to provide more accurate prediction. Our study indicates that the posterior probability of a correct prediction could serve as one of the key measures.

Amino Acid Sequence↗
PubMed1986

Genetically essential and nonessential alpha-tubulin genes specify functionally interchangeable proteins.

Microtubules in yeast are essential components of the mitotic and meiotic spindles and are essential for nuclear movement during cell division and mating. The relative importance in these processes of the two divergent alpha-tubulin genes of the budding yeast Saccharomyces cerevisiae, TUB1 and TUB3, was examined through the construction of null mutations and by increasing their copy number on chromosomes and on plasmids. Experiments with null alleles of TUB3 showed that TUB3 was not essential for mitosis, meiosis, or mating. Null alleles of TUB3, however, did cause several phenotypes, including hypersensitivity to the antimicrotubule drug benomyl and poor spore viability. On the other hand, the TUB1 gene was essential for growth of normal haploid cells. Even in diploids heterozygous for a TUB1 null allele, several dominant phenotypes were evident, including slow growth and poor sporulation. This functional difference between the two genes is apparently due to different levels of expression, because extra copies of either gene could suppress the defects caused by a null mutation in the other. We conclude that in spite of the 10% divergence between the products of the two genes, there is no essential qualitative functional difference between them.

Alleles↗
PubMed2004

In vivo gene transfer into the adult honeybee brain by using electroporation.

The honeybee, Apis mellifera L., is a social insect and they show wide variety of exquisite social behaviors to maintain colony activity. To enable the elucidation of those social behaviors at a molecular level and gene function in the nervous system, we developed an in vivo method to perform gene transfer in the adult brain of living honeybee by electroporation. When green fluorescent protein-expressing plasmid was transferred to the brain with this system, green fluorescence was observed near the anode location. The expression of transfected genes was confirmed at both transcriptional and translational levels by reverse transcription-polymerase chain reaction and immunoblot analyses. This system will facilitate the analysis of gene function and the regulatory mechanisms of gene networks in the nervous system and provide clues to clarify the relation between those genes and the complex behaviors of the honeybee.

Animals↗
PubMed2002

[Comparative genomics and proteomics of Drosophila, Brenner's nematode, and Arabidopsis: identification of functionally similar genes and proteins of meiotic chromosome synapsis].

The published principles of computer analysis of genomes and protein sets in taxonomically distant eukaryotes are expounded. The authors developed a search strategy to identify in genomes of such organisms genes and proteins nonhomologous in primary structure but having similar functions in cells dividing by meiosis. This strategy based on the combined principles of genomics, proteomics, and morphometric analysis of subcellular structures was applied to a computer search for genes encoding the proteins of synaptonemal complexes in genomes of Drosophila melanogaster, the nematode Caenorhabditis elegans, and the plant Arabidopsis thaliana. These proteins proved to be functionally similar to their counterparts in yeast Saccharomyces cerevisiae (protein Zip1p) and mammals (protein SCP1).

Animals↗
PubMed2003

Gene profiling of a myeloma cell line reveals similarities and unique signatures among IL-6 response, N-ras-activating mutations, and coculture with bone marrow stromal cells.

ANBL-6, a myeloma cell line, proliferates in response to interleukin 6 (IL-6) stimulation, coculture with bone marrow stromal cells, and when harboring a constitutively active mutant N-ras gene. Eighteen samples, including 4 IL-6-treated, 3 mutant N-ras-transfected, 3 normal stroma-stimulated, 2 multiple myeloma (MM) stroma-stimulated, and 6 untreated controls were profiled using microarrays interrogating 12 626 genes. Global hierarchical clustering analysis distinguished at least 6 unique expression signatures. Notably, the different stimuli altered distinct functional gene programs. Class comparison analysis (P =.001) revealed 138 genes (54% involved in cell cycle) that distinguished IL-6-stimulated versus nontreated samples. Eighty-seven genes distinguished stroma-stimulated versus IL-6-treated samples (22% encoded for extracellular matrix [ECM] proteins). A total of 130 genes distinguished N-ras transfectants versus IL-6-treated samples (26% involved in metabolism). A total of 157 genes, 20% of these involved in signaling, distinguished N-ras from stroma-interacting samples. All 3 stimuli shared 347 genes, mostly of metabolic function. Genes that distinguished MM1 from MM4 clinical groups were induced at least by one treatment. Notably, only 3 genes (ETV5, DUSP6, and KIAA0735) are uniquely induced in mutant ras-containing cells. We have demonstrated gene expression patterns in myeloma cells that distinguish an intrinsic genetic transformation event and patterns derived from both soluble factors and cell contacts in the bone marrow microenvironment.

Bone Marrow Cells↗
PubMed1994

Functional evidence for a second tumor suppressor gene on human chromosome 17.

The development and progression of human tumors often involves inactivation of tumor suppressor gene function. Observations that specific chromosome deletions correlate with distinct groups of cancer suggest that some types of tumors may share common defective tumor suppressor genes. In support of this notion, our initial studies showed that four human carcinoma cell lines belong to the same complementation group for tumorigenic potential. In this investigation, we have extended these studies to six human soft tissue sarcoma cell lines. Our data showed that hybrid cells between a peripheral neuroepithelioma (PNET) cell line and normal human fibroblasts or HeLa cells were nontumorigenic. However, hybrid cells between the PNET cell line and five other soft tissue sarcoma cell lines remained highly tumorigenic, suggesting at least one common genetic defect in the control of tumorigenic potential in these cells. To determine the location of this common tumor suppressor gene, we examined biochemical and molecular polymorphic markers in matched pairs of tumorigenic and nontumorigenic hybrid cells between the PNET cell line and a normal human fibroblast. The data showed that loss of the fibroblast-derived chromosome 17 correlated with the conversion from nontumorigenic to tumorigenic cells. Transfer of two different chromosome 17s containing a mutant form of the p53 gene into the PNET cell line caused suppression of tumorigenic potential, implying the presence of a second tumor suppressor gene on chromosome 17.

Animals↗
PubMed2005

A high-throughput gene-silencing system for the functional assessment of defense-related genes in barley epidermal cells.

Large-scale gene silencing by RNA interference (RNAi) offers the possibility to address gene function in eukaryotic organisms at a depth unprecedented until recently. Although genome-wide RNAi approaches are being carried out in organisms like Caenorhabditis elegans, Drosophila spp. or human after the corresponding tools had been developed, knock-down of only single or a few genes by RNAi has been reported in plants thus far. Here, we present a method for high-throughput, transient-induced gene silencing (TIGS) by RNAi in barley epidermal cells that is based on biolistic transgene delivery. This method will be useful to address gene function of shoot epidermis resulting in cell-autonomous phenotypes such as resistance or susceptibility to the powdery-mildew fungus Blumeria graminis f. sp. hordei. Gene function in epidermal cell elongation, stomata regulation, or UV resistance might be addressed as well. Libraries of RNAi constructs can be built up by a new, cost-efficient method that combines highly efficient ligation and recombination by the Gateway cloning system. This method allows cloning of any blunt-ended DNA fragment without the need of adaptor sequences. The final RNAi destination vector was found to direct highly efficient RNAi, as reflected by complete knock-down of a cotransformed green fluorescent protein reporter gene as well as by complete phenolcopy of the recessive loss-of-function mlo resistance gene. By using this method, a role of the t-SNARE protein HvSNAP34 in three types of durable, race-nonspecific resistance was observed.

Gene Expression Profiling↗
PubMed1998

TNF-alpha and IFN-gamma down-regulate the expression of the metastasis-associated bi-functional 37LRP/p40 gene and protein in transformed keratinocytes.

The 37 LRP/p40 molecule is a bi-functional protein in which expression is increased in a large variety of cancers in association with their metastatic phenotype. Here we present the first data concerning the 37 LRP/p40 gene promoter activity and show that it is very active in a cervix carcinoma cell line. Interestingly, despite hallmarks of a housekeeping gene, we show that the 37 LRP/p40 gene promoter can be down-regulated by two potentially anticancerous cytokines, TNF-alpha and IFN-gamma. In addition, the dual fate of the protein, i.e., being intracellularly involved in the cell translation machinery and incorporated into a 67-kDa cell surface protein functioning as a laminin receptor (67LR), is differentially affected by the treatment. Our data suggest multiple regulation levels in the control of the 67LR/37LRP/p40 molecule expression and uncover new clues for the understanding of both the control of expression of this metastasis-associated molecule and the IFN-gamma and TNF-alpha anticancerous action.

Cell Line, Transformed↗
PubMed1998

Chloroplast division in higher plants requires members of two functionally divergent gene families with homology to bacterial ftsZ.

The division of plastids is critical for viability in photosynthetic eukaryotes, but the mechanisms associated with this process are still poorly understood. We previously identified a nuclear gene from Arabidopsis encoding a chloroplast-localized homolog of the bacterial cell division protein FtsZ, an essential cytoskeletal component of the prokaryotic cell division apparatus. Here, we report the identification of a second nuclear-encoded FtsZ-type protein from Arabidopsis that does not contain a chloroplast targeting sequence or other obvious sorting signals and is not imported into isolated chloroplasts, which strongly suggests that it is localized in the cytosol. We further demonstrate using antisense technology that inhibiting expression of either Arabidopsis FtsZ gene (AtFtsZ1-1 or AtFtsZ2-1) in transgenic plants reduces the number of chloroplasts in mature leaf cells from 100 to one, indicating that both genes are essential for division of higher plant chloroplasts but that each plays a distinct role in the process. Analysis of currently available plant FtsZ sequences further suggests that two functionally divergent FtsZ gene families encoding differentially localized products participate in chloroplast division. Our results provide evidence that both chloroplastic and cytosolic forms of FtsZ are involved in chloroplast division in higher plants and imply that important differences exist between chloroplasts and prokaryotes with regard to the roles played by FtsZ proteins in the division process.

Amino Acid Sequence↗
PubMed1994

Genomic structure and chromosomal localization of processed pseudogenes for human RBP-Jk.

The functional gene for human recombination signal sequence-binding protein (RBP-Jk) and corresponding processed psudogenes have been isolated from various species, such as Drosophila, Xenopus, mouse, and human. Here we report the isolation of another two genomic pseudogenes of human RBP-Jk, named K2 and K7, from a cosmid library of Hela cells. The nucleotide sequences of both genes exhibited more than 95% homology to the functional human gene for RBP-Jk. Moreover, they did not contain any intron sequences and were interrupted by several stop codons in all frames. In situ hybridization demonstrated that the pseudogenes, K2 and K7, were localized at chromosomes 9p13 and 9q13, respectively. Their physical maps differed from those of the true functional gene and of the pseudogenes reported previously by Amakawa et al. (1993).

Base Sequence↗