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Results for “Functional potential”

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At least 235 records · Page 13Linked to original sources

PubMed2004

Multiple ATP-hydrolyzing sites that potentially function in cytoplasmic dynein.

Cytoplasmic dynein is a minus-end-directed microtubule motor involved in numerous essential processes within eukaryotic cells, such as nuclear segregation and trafficking of intracellular particles. The motor domain of the dynein heavy chain comprises six tandemly linked AAA (ATPase associated with diverse cellular activities) modules (AAA1-AAA6). The first four modules include nucleotide-binding sites (Walker A or P-loop motifs), and each of the four sites appears to bind ATP. However, the role and the function of each binding site are unknown. Especially, the question of which P-loops are ATP-hydrolyzing sites has not been answered, because it is difficult to measure the ATPase activity of each P-loop. Here, we purified several truncated Saccharomyces cerevisiae cytoplasmic dynein fragments and their mutants expressed in Escherichia coli and then measured their ATPase activities. Our results suggest that there are multiple ATP-binding sites that have abilities to hydrolyze ATP in cytoplasmic dynein. Furthermore, a single AAA module is insufficient for ATP hydrolysis, and the adjacent module facing the ATP-binding site is necessary for ATP-hydrolyzing activity.

Adenosine Triphosphate↗

PubMed1983

T cells discriminate between Ia antigens expressed on allogeneic accessory cells and B cells: a potential function for carbohydrate side chains on Ia molecules.

Previous studies have shown that the peptides obtained from accessory cell and B-cell Ia molecules are identical but that the alpha chains of B-cell Ia molecules are more extensively sialylated than those of accessory cells. The present studies were designed to determine whether this glycosylation difference can account for the functional difference in the capacity of the two cell types to activate alloreactive T cells. The experimental data show that normal resting B cells lack the capacity to induce DNA synthesis or differentiation in alloreactive T cells. T cells do recognize polymorphisms in B-cell Ia molecules, however, because they can be specifically primed for a subsequent proliferative stimulus of the same haplotype. The mitogenic signal for T cells is delivered by either allogeneic accessory cells or neuraminidase-treated B cells. Therefore, the T-cell receptor(s) may contain a site specific for the nonpolymorphic asialocarbohydrate moiety on the alpha chains of accessory cell Ia molecules.

Animals↗

PubMed1997

Specific interactions and potential functions of human TAFII100.

Human transcription initiation factor TFIID contains the TATA-binding protein (TBP) and several TBP-associated factors (TAFs). To investigate the structural organization and function of TFIID, we have cloned and expressed a DNA encoding the third largest human TFIID subunit, hTAFII100. Immunoprecipitation studies demonstrate that hTAFII100 is an integral subunit that is associated with all transcriptionally-competent forms of TFIID. They further suggest that at least part of the N-terminal region lies on the surface of TFIID, while a C-terminal region containing conserved WD-40 repeats appears inaccessible. Both in vivo and in vitro assays indicate that hTAFII100 interacts strongly with the histone H4-related hTAFII80 and the histone H3-related hTAFII31, as well as a stable complex comprised of both hTAFII80 and hTAFII31. Apparently weaker interactions of hTAFII100 with TBP, hTAFII250, hTAFII28, and hTAFII20, but not hTAFII55, also have been observed. These results suggest a role for hTAFII100 in stabilizing interactions of TAFs, especially the histone-like TAFs, in TFIID. In addition, functional studies show that anti-hTAFII100 antibodies selectively inhibit basal transcription from a TATA-less initiator-containing promoter, relative to a TATA-containing promoter, suggesting a possible core promoter-specific function for hTAFII100.

Amino Acid Sequence↗

PubMed1999

A human papillomavirus E2 transcriptional activator. The interactions with cellular splicing factors and potential function in pre-mRNA processing.

The human papillomavirus (HPV) E2 protein plays an important role in transcriptional regulation of viral genes as well as in viral DNA replication. Unlike most types of HPV, the E2 protein of epidermodysplasia verruciformis (EV)-associated HPVs harbors a relatively long hinged region between the terminal, conserved transactivation and DNA binding/dimerization domains. The sequence of EV-HPV E2 hinge contains multiple arginine/serine (RS) dipeptide repeats which are characteristic of a family of pre-messenger RNA splicing factors, called SR proteins. Here we show that the HPV-5 (an EV-HPV) E2 protein can specifically interact with cellular splicing factors including a set of prototypical SR proteins and two snRNP-associated proteins. Transiently expressed HPV-5 E2 protein colocalizes with a nuclear matrix associated-splicing coactivator in nuclear speckled domains. The RS-rich hinge is essential for E2 transactivator interaction with splicing factors and for its subnuclear localization. Moreover, we present functional evidence for the HPV-5 E2 transactivator, which shows that the RS-rich hinge domain of the E2 protein can facilitate the splicing of precursor messenger RNA made via transactivation by E2 itself. Our results, therefore, suggest that a DNA binding transactivator containing an RS-rich sequence can play a dual role in gene expression.

Gene Expression Regulation↗

PubMedDate not supplied

The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review).

During the last 2 years, several novel genes that encode glucose transporter-like proteins have been identified and characterized. Because of their sequence similarity with GLUT1, these genes appear to belong to the family of solute carriers 2A (SLC2A, protein symbol GLUT). Sequence comparisons of all 13 family members allow the definition of characteristic sugar/polyol transporter signatures: (1) the presence of 12 membrane-spanning helices, (2) seven conserved glycine residues in the helices, (3) several basic and acidic residues at the intracellular surface of the proteins, (4) two conserved tryptophan residues, and (5) two conserved tyrosine residues. On the basis of sequence similarities and characteristic elements, the extended GLUT family can be divided into three subfamilies, namely class I (the previously known glucose transporters GLUT1-4), class II (the previously known fructose transporter GLUT5, the GLUT7, GLUT9 and GLUT11), and class III (GLUT6, 8, 10, 12, and the myo-inositol transporter HMIT1). Functional characteristics have been reported for some of the novel GLUTs. Like GLUT1-4, they exhibit a tissue/cell-specific expression (GLUT6, leukocytes, brain; GLUT8, testis, blastocysts, brain, muscle, adipocytes; GLUT9, liver, kidney; GLUT10, liver, pancreas; GLUT11, heart, skeletal muscle). GLUT6 and GLUT8 appear to be regulated by sub-cellular redistribution, because they are targeted to intra-cellular compartments by dileucine motifs in a dynamin dependent manner. Sugar transport has been reported for GLUT6, 8, and 11; HMIT1 has been shown to be a H+/myo-inositol co-transporter. Thus, the members of the extended GLUT family exhibit a surprisingly diverse substrate specificity, and the definition of sequence elements determining this substrate specificity will require a full functional characterization of all members.

Amino Acid Motifs↗

PubMed1993

Potentially functional regions of nucleic acids recognized by a Kohonen's self-organizing map.

Computer recognition of short functional sites on DNA, such as promoter regions or intron-exon boundaries, has recently attracted much interest. In this paper we have focused our attention on the automatic recognition of relevant features of human nucleic acid sequences by means of an unsupervised artificial neural network model. Sixty messenger RNA and 31 genomic DNA sequences were analysed. The results showed that in mRNA, the minimal similarity 60 base pattern was guanine- and cytosine-rich and located in most sequences in a range of 250 bases from either the middle point of the signal peptide coding region or from the start of the coding region. On DNA sequences a region defined by a cluster of minimal similarity patterns was present in many of the analysed genes. This zone may be related to alternative splicing and DNA methylation.

Algorithms↗

PubMed2002

Serine phosphorylation of RUNX2 with novel potential functions as negative regulatory mechanisms.

The RUNX family represents a small group of heterodimeric transcription factors that master-regulate osteogenesis and hematopoiesis in mammals. Their genetic defects cause human diseases such as cleidocranial dysplasia (CCD) and acute myelogenous leukemia. However, the mechanism(s) regulating their functions are still poorly understood. Here, we report a novel observation that suggests that the osteogenesis-associated homologue RUNX2 is negatively regulated by the phosphorylation of two conserved serines (S104 and S451) in two distinct functional aspects. The phosphorylation of S104 could abolish the heterodimerization of RUNX2 with the partner subunit, PEBP2beta, which enhances the metabolic stability of RUNX2. On the other hand, the phosphorylation of S451 resides within the C-terminal transcription inhibition domain of RUNX2 and hence is implicated in its functional mobilization. One CCD mutation, S104R of RUNX2, appears to mimic the phosphorylation-dependent inhibition of heterodimerization, thereby rendering RUNX2 metabolically unstable.

Amino Acid Sequence↗

PubMed1997

Sequence analysis, identification of evolutionary conserved motifs and expression analysis of murine tcof1 provide further evidence for a potential function for the gene and its human homologue, TCOF1.

The gene mutated in Treacher Collins syndrome, an autosomal dominant disorder of facial development, has recently been cloned. While the function of the predicted protein, Treacle, is unknown, it has been shown to share a number of features with the highly phosphorylated nucleolar phosphoproteins, which play a role in nucleolar-cytoplasmic transport. In the current study, the murine homologue of the Treacher Collins syndrome gene has been isolated and shown to encode a low complexity, serine/alanine-rich protein of 133 kDa. Interspecies comparison indicates that the proteins display 61.5% identity, with the level of conservation being greatest in the regions of acidic/basic amino acid repeats and nuclear localization signals. These features are shared with the nucleolar phosphoproteins. Confirmation that the gene isolated in the current study is orthologous with the Treacher Collins syndrome gene was provided by the demonstration that it mapped to central mouse chromosome 18 in a conserved syntenic region with human chromosome 5q21-q33. Expression analysis in the mouse indicated that the gene was expressed in a wide variety of embryonic and adult tissues. Peak levels of expression in the developing embryo were observed at the edges of the neural folds immediately prior to fusion, and also in the developing branchial arches at the times of critical morphogenetic events. These observations support a role for the gene in the development of the craniofacial complex and provide further evidence that the gene encodes a protein which may be involved in nucleolar-cytoplasmic transport.

Amino Acid Sequence↗

PubMed2006

Expression and potential function of cathelicidin antimicrobial peptides in dermatophytosis and tinea versicolor.

OBJECTIVES: This study was designed to characterize the role of the human cathelicidin LL-37 in fungal skin infections such as dermatophytosis and tinea versicolor. METHODS: The in vitro antimicrobial activity of synthetic antimicrobial peptides including the human cathelicidin LL-37 against Malassezia furfur and several dermatophytes was determined. Immunostaining was performed to determine expression of cathelicidin in skin biopsies from patients with tinea pedis, tinea corporis and tinea versicolor. Cathelicidin peptide expression was evaluated by western blotting and mRNA expression was studied in keratinocytes exposed to M. furfur or Trichophyton rubrum. RESULTS: LL-37 inhibits the growth of fungi with an MIC of 20-30 microM for M. furfur and 12.5 microM for Trichophyton mentagrophytes and T. rubrum. LL-37 also shows fungicidal activity with a minimum fungicidal concentration (MFC) of 12.5 and 25 microM for T. mentagrophytes and T. rubrum, respectively. An increase in cathelicidin expression was observed in human skin tissue infected with fungi compared with healthy skin. Western blotting of skin scrapings demonstrated that human cathelicidin is processed from its precursor into an active peptide in both healthy and infected plantar skin. CONCLUSIONS: These findings support a hypothesis that antimicrobial peptides such as cathelicidins can play a role in skin defence against dermatophytes and M. furfur.

Adult↗

PubMed1997

Genomic imprinting: potential function and mechanisms revealed by the Prader-Willi and Angelman syndromes.

The Prader-Willi (PWS) and Angelman (AS) syndromes are two clinically distinct syndromes which result from lack of expression of imprinted genes within chromosome 15q11-q13. These two syndromes result from 15q11-q13 deletions, chromosome 15 uniparental disomy (UPD), imprinting centre mutations and, for AS, probable mutations in a single gene. The differential phenotype results from a paternal genetic deficiency in PWS patients and a maternal genetic deficiency in AS patients. Within 15q11-q13, four genes (SNRPN, IPW, ZNF127, FNZ127) and two expressed sequence tags (PAR1 and PAR5) have been found to be expressed only from the paternally inherited chromosome, and therefore all must be considered candidate genes involved in the pathogenesis of PWS. A candidate AS gene (UBE3A) has very recently been identified. The mechanisms of imprinted gene expression are not yet understood, but it is clear that DNA methylation is involved in both somatic cell expression and inheritance of the imprint. The presence of DNA methylation imprints that distinguish the paternally and maternally inherited alleles is a common characteristic of all known imprinted genes which have been studied extensively, including SNRPN and ZNF127. Recently, several PWS and AS patients have been found that have microdeletions in a region upstream of the SNRPN gene referred to as the imprinting centre, or IC. Paternal IC deletions in PWS patients and maternal IC deletions in AS patients result in uniparental DNA methylation and uniparental gene expression at biparentally inherited loci. The IC is a novel genetic element which controls initial resetting of the parental imprint in the germline for all imprinted gene expression over a 1.5-2.5 Mb region within chromosome 15q11-q13.

Angelman Syndrome↗

PubMed2005

Expression of gastrin releasing Peptide receptor in renal cell carcinomas: a potential function for the regulation of neoangiogenesis and microvascular perfusion.

PURPOSE: Gastrin releasing peptide (GRP) is a growth factor for renal cell carcinoma (RCC) and it has vasoactive properties. Blockade of GRP receptor inhibits the growth of GRP receptor positive and negative tumors in nude mice, suggesting GRP effects other than those related to tumor epithelium. Therefore, in this study we analyzed the effects of GRP receptor blockade on neoangiogenesis in RCC. MATERIALS AND METHODS: GRP receptor expression was determined in human RCC and corresponding normal tissue by real-time reverse transcriptase-polymerase chain reaction, immunohistochemistry and confocal laser scanning microscopy. Multicellular spheroids of the A498 RCC line were implanted into dorsal skin fold chambers of athymic nude mice. Neoangiogenesis was measured by intravital microscopy after blockade of GRP receptors by the GRP antagonist RC-3095. The influence of GRP on vascular endothelial growth factor secretion in A498 cells was studied in vitro. RESULTS: GRP receptor expression was immunolocalized in tumor cells and microvessels. Implanted tumor cell spheroids and spheroid microvessels of the chamber also expressed GRP receptors. Spheroid neoangiogenesis was significantly inhibited by RC-3095 when given immediately after spheroid implantation. Vascular endothelial growth factor secretion of A498 cells was not affected by GRP. CONCLUSIONS: RCC angiogenesis is sensitive to GRP receptor blockade. Therefore, GRP receptors may not only stimulate tumor cell proliferation, but also affect tumor microcirculation.

Animals↗

PubMed1993

Spacing and orientation of bipartite DNA-binding motifs as potential functional determinants for POU domain factors.

Investigation of the large POU domain family of developmental regulators has revealed a molecular mechanism by which highly related transcription factors sharing common DNA-binding motifs act to functionally discriminate their cognate DNA sequences. Studies of two classes of neuron-specific POU domain factors (III and IV) indicate that functional specificity on their native response elements is achieved by accommodating different nucleotide spacing between variably oriented bipartite core DNA-binding motifs. The preferred orientation of the POU-specific domain of the neuronal factors on their native response elements appears to be opposite that of Pit-1 and Oct-1. Members of POU-III (Brn-2) class exhibit remarkable flexibility in DNA site recognition (tolerating core motifs spaced by 0, 2, or 3 nucleotides), whereas POU-IV (Brn-3) class is highly constrained (tolerating core motifs with a spacing of 3 nucleotides). The molecular determinant of the constraint in DNA site selection appears to be imparted by 3 amino acid residues in the amino-terminal basic region in concert, with helix 2 of the POU homeo domain which together are involved in minor groove and possibly phosphate backbone contacts. Similar mechanisms may underlie differential flexibility in spacing and orientation for diverse families of transcription factors.

Amino Acid Sequence↗

PubMed1985