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

TFE3 is a ubiquitously expressed member of the TFE3/mi family of basic helix loop helix zipper transcription factors. TFE3 binds to muE3 sites located in the immunoglobulin heavy-chain (IgH) intronic enhancer, heavy-chain variable region promoters, the Ig kappa intronic enhancer, and regulatory sites in other genes. To understand the role of TFE3 in Ig expression and lymphoid development, we used embryonic stem (ES) cell-mediated gene targeting and RAG2-/- blastocyst complementation to generate mice which lack TFE3 in their B and T lymphocytes. TFE3- ES cells fully reconstitute the B- and T-cell compartments, giving rise to normal patterns of IgM+ B220+ B cells and CD4+ and CD8+ T cells. However, TFE3- B cells show several defects consistent with poor B-cell activation. Serum IgM levels are reduced twofold and IgG and IgA isotypes are reduced three- to sixfold in the TFE3- chimeras even though in vitro, the TFE3- splenocytes secrete normal levels of all isotypes in response to lipopolysaccharide activation. Peripheral TFE3- B cells also show reduced surface expression of CD23 and CD24 (heat-stable antigen).
Mol Cell Biol 1997 Jun
PMID:The absence of the transcription activator TFE3 impairs activation of B cells in vivo. 915 32

Fos-related antigen 2 (Fra-2) is a member of the Fos family of immediate-early genes, most of which are rapidly induced by second messengers. All members of this family act by binding to AP-1 sites as heterodimeric complexes with other proteins. However, each appears to have a distinct role. The role and biology of Fra-2 are less well understood than those of its relatives c-Fos, Fra-1, and FosB; moreover, Fra-2 target genes remain largely unknown, as does the basis of its selective effects on transcriptional activity. To pursue these issues, we created a transgenic rat line (NATDNF2) in which a dominant negative fra-2 (DNF2) gene is strongly expressed in the pineal gland; tissue selectivity was achieved by putting the DNF2 gene under the control of the rat arylalkylamine N-acetyltransferase (AANAT) regulatory region, which targets gene expression to a very restricted set of tissues (pineal gland >> retina). Expression of AANAT is normally turned on after the onset of darkness in the rat; as a result, pineal DNF2 expression occurs only at night. This was associated with marked suppression of the nocturnal increase in fra-2 mRNA and protein levels, indicating that DNF2 expression inhibits downstream effects of Fra-2, including the maintenance of high levels of fra-2 gene expression. Analysis of 1,190 genes in the NATDNF2 pineal gland, including the AANAT gene, identified two whose expression is strongly linked to fra-2 expression: the genes encoding type II iodothyronine deiodinase and nectadrin (CD24).
Mol Cell Biol 2001 Jun
PMID:Tissue-specific transgenic knockdown of Fos-related antigen 2 (Fra-2) expression mediated by dominant negative Fra-2. 1134 Jan 64

The increase in eosinophils at the site of antigen challenge has been used as evidence to suggest that this cell type plays a role in the pathophysiology of asthma. Aberrant production of several different cytokines, particularly interleukin (IL)-5, has been shown to result in eosinophilia. IL-5 influences the development and maturation of eosinophils in a number of different ways. Of note is the ability of IL-5 to act as a survival factor for eosinophils specifically inhibiting apoptosis. The precise mechanism by which IL-5 exerts its effect remains obscure. We used microarray technologies to investigate the changes in the messenger RNA expression profile of eosinophils after treatment with IL-5. Using the Affymetrix Hu6800 chip, a total of 80 genes were observed to be regulated by 2-fold or greater. Many of the genes previously identified as regulated by IL-5 were regulated in our microarray experiments. Of the 73 genes found to be upregulated, many were shown to play a role in adhesion, migration, activation, or survival of eosinophils or hematopoietic cells, whereas the function of others was unknown. To facilitate the identification of genes that govern the apoptosis and survivability of eosinophils, we used an alternative cellular model, TF1.8 cells, whose survival was also dependent on IL-5. Comparison of these models identified four genes, Pim-1, DSP-5 (hVH3, B23), CD24, and SLP-76, whose regulation was similarly coordinated in both systems. Identification of Pim-1 and SLP-76 as regulated by IL-5 led us to suggest a direct role for these proteins in the IL-5 signaling pathway in eosinophils. The tissue distribution of these genes demonstrated that Pim-1 and SLP-76 were relatively restricted to the eosinophil compared with their expression in brain, bone marrow, kidney, liver, and lung. By contrast, DSP-5 and CD24 were confirmed as ubiquitous in their expression by microarray.
Am J Respir Cell Mol Biol 2001 Oct
PMID:Microarray analysis of eosinophils reveals a number of candidate survival and apoptosis genes. 1169 44

Because interleukin (IL)-5 family cytokines are critical regulators of eosinophil development, recruitment, and activation, this study was initiated to identify proteins induced by these cytokines in eosinophils. Using oligonucleotide microarrays, numerous transcripts were identified as responsive to both IL-5 and granulocyte macrophage-colony-stimulating factor (GM-CSF), but no transcripts were markedly affected by one cytokine and not the other. Expression of several gene products were seen to be increased following in vitro stimulation of human blood eosinophils, including the IL-3 receptor alpha subunit, lymphotoxin beta, Pim-1, and cyclin D3. Given that eosinophils recovered from the bronchoalveolar lavage fluid of allergic patients after antigen challenge are exposed to IL-5 or GM-CSF in the airway prior to isolation, the hypothesis was tested that selected IL-5- and GM-CSF-responsive genes are upregulated in airway eosinophils relative to the expression in blood cells. Airway eosinophils displayed greater cell surface expression of the IL-3 receptor alpha subunit, CD44, CD25, and CD66e, suggesting that these proteins may be markers of eosinophil activation by IL-5 family cytokines in airway eosinophils. Other genes that were induced by both IL-5 and GM-CSF showed protein expression at similar or decreased levels in airway eosinophils relative to their circulating counterparts (i.e., lymphotoxin beta and CD24). These studies have identified several transcriptional targets of IL-5 and GM-CSF in human eosinophils and suggest that a number of protein products are critical to the responsiveness of airway eosinophils.
Am J Respir Cell Mol Biol 2004 May
PMID:Expression of interleukin-5- and granulocyte macrophage-colony-stimulating factor-responsive genes in blood and airway eosinophils. 1463 Jun 12

CD24 is a molecule that recently has raised considerable attention in tumour biology. It is involved in cell adhesion and metastatic tumour spread. It has also been described as a new diagnostic marker of tumours, of neuroendocrine differentiation and, possibly most intriguing of all, of patient prognosis. High rates of CD24 expression detected by immunohistochemistry have been found in epithelial ovarian cancer (83%), breast cancer (85%), non-small cell lung cancer (45%), prostate cancer (48%) and pancreatic cancer (72%). With the exception of pancreatic cancer, high rates of CD24 are significantly associated with a more aggressive course of the disease, a finding that remains significant in a multivariate analysis. The aim of this review is to summarize relevant work covering these aspects of CD24.
J Mol Histol 2004 Mar
PMID:Tumour biological aspects of CD24, a mucin-like adhesion molecule. 1533 45

Earthworm innate immunity depends upon small and large leukocytes (coelomocytes) that synthesize and secrete humoral antimicrobial molecules (e.g. lysenin, fetidin, eiseniapore, coelomic cytolytic factor [CCF]; Lumbricin I). Small coelomocytes (cytotoxic) are positive (CD11a, CD45RA, CD45RO, CDw49b, CD54, beta(2)-m and Thy-1 [CD90]; CD24; TNF-alpha) but negative using other mammalian markers. Large coelomocytes (phagocytic) are uniformly negative. Specific earthworm anti-EFCC 1, 2, 3, 4 mAbs are negative for Drosophila melanogaster hemocytes and mammalian cells but positive those of earthworms. Coelomocytes contain several lysosomal enzymes involved in phagocytosis and a pattern recognition molecule (CCF) that may trigger the prophenoloxidase cascade a crucial innate immune response. Earthworms and other invertebrates possess natural, non-specific, non-clonal, and non-anticipatory immune response governed by germ line genes. Toll and Toll-like receptor signaling is essential for phagocytosis and antimicrobial peptide synthesis and secretion in insects and vertebrates but has not yet been shown to be essential in earthworm innate responses.
Mol Immunol 2005 May
PMID:Anticipating innate immunity without a Toll. 1582 85

Stable and safe corrective gene transfer in stem keratinocytes is necessary for ensuring success in cutaneous gene therapy. There have been numerous encouraging preclinical approaches to cutaneous gene therapy in the past decade, but it is only recently that a human volunteer suffering from junctional epidermolysis bullosa could be successfully grafted using his own non-selected, genetically corrected epidermal keratinocytes. However, ex vivo correction of cancer-prone genetic disorders necessitates a totally pure population of stably transduced stem keratinocytes for grafting. Antibiotic selection is not compatible with the need for full respect for natural cell fate potential and avoidance of immunogenic response in vivo. In order to surmount these problems, we developed a strategy for selecting genetically modified stem cell keratinocytes. Driving ectopic expression of CD24 (a marker of post-mitotic keratinocytes) at the surface of clonogenic keratinocytes permitted their full selection. Engineered keratinocytes expressing CD24 and the green fluorescent protein (GFP) tracer gene were shown to retain their original growth and differentiation potentials both in vitro and in vivo over 300 generations. Also, they did not exhibit signs of genetic instability. Using ectopic expression of CD24 as a selective marker of genetically modified human epidermal stem cells appears to be the first realistic approach to safe cutaneous gene therapy in cancer-prone disease conditions.
Mol Ther 2007 Dec
PMID:Safe selection of genetically manipulated human primary keratinocytes with very high growth potential using CD24. 1771 30

Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44(+)CD24(-/low) population. The use of oncolytic adenoviruses presents an attractive anti-tumor approach for eradication of these cells because their entry occurs through infection and they are, therefore, not susceptible to those mechanisms that commonly render stem cells resistant to many drugs. We isolated CD44(+)CD24(-/low) cells from patient pleural effusions and confirmed stem cell-like features including oct4 and sox2 expression and Hoechst 33342 exclusion. CD44(+)CD24(-/low) cells, including the Hoechst excluding subpopulation, could be effectively killed by oncolytic adenoviruses Ad5/3-Delta24 and Ad5.pk7-Delta24. In mice, CD44(+)CD24(-/low) cells formed orthotopic breast tumors but virus infection prevented tumor formation. Ad5/3-Delta24 and Ad5.pk7-Delta24 were effective against advanced orthotopic CD44(+)CD24(-/low)-derived tumors. In summary, Ad5/3-Delta24 and Ad5.pk7-Delta24 can kill CD44(+)CD24(-/low), and also committed breast cancer cells, making them promising agents for treatment of breast cancer.
Mol Ther 2007 Dec
PMID:Oncolytic adenoviruses kill breast cancer initiating CD44+CD24-/low cells. 1802 82

The RNA-binding protein Musashi1 (Msi1) is a positive regulator of Notch-mediated transcription in Drosophila melanogaster and neural progenitor cells and has been identified as a putative human breast stem cell marker. Here we describe a novel functional role for Msi1: its ability to drive progenitor cell expansion along the luminal and myoepithelial lineages. Expression of Msi1 in mammary epithelial cells increases the abundance of CD24(hi) Sca-1(+), CD24(hi) CD29(+), CK19, CK6, and double-positive CK14/CK18 progenitor cells. Proliferation is associated with increased proliferin-1 (PLF1) and reduced Dickkopf-3 (DKK3) secretion into the conditioned medium from Msi-expressing cells, which is associated with increased colony formation and extracellular signal-regulated kinase (ERK) phosphorylation. Treatment with the MEK inhibitor U0126 inhibits ERK activation and decreases Notch and beta-catenin/T-cell factor (TCF) reporter activity resulting from Msi1 expression. Reduction of DKK3 in control cells with a short hairpin RNA (shRNA) increases Notch and beta-catenin/TCF activation, whereas reduction of PLF1 with a shRNA in Msi1-expressing cells inhibits these pathways. These results identify Msi1 as a key determinant of the mammary lineage through its ability to coordinate cell cycle entry and activate the Notch and Wnt pathways by a novel autocrine process involving PLF1 and DKK3.
Mol Cell Biol 2008 Jun
PMID:Musashi1 modulates mammary progenitor cell expansion through proliferin-mediated activation of the Wnt and Notch pathways. 1836 62

Stem cells are self-renewing multipotent progenitors with the broadest developmental potential in a given tissue at a given time. Normal stem cells in the adult organism are responsible for renewal and repair of aged or damaged tissue. Adult stem cells are present in virtually all tissues and during most stages of development. In this review, we introduce the reader to the basic information about the field. We describe selected stem cell isolation techniques and stem cell markers for various stem cell populations. These include makers for endothelial progenitor cells (CD146/MCAM/MUC18/S-endo-1, CD34, CD133/prominin, Tie-2, Flk1/KD/VEGFR2), hematopoietic stem cells (CD34, CD117/c-Kit, Sca1), mesenchymal stem cells (CD146/MCAM/MUC18/S-endo-1, STRO-1, Thy-1), neural stem cells (CD133/prominin, nestin, NCAM), mammary stem cells (CD24, CD29, Sca1), and intestinal stem cells (NCAM, CD34, Thy-1, CD117/c-Kit, Flt-3). Separate section provides a concise summary of recent clinical trials involving stem cells directed towards improvement of a damaged myocardium. In the last part of the review, we reflect on the field and on future developments.
J Mol Med (Berl) 2008 Dec
PMID:Adult stem cells and their trans-differentiation potential--perspectives and therapeutic applications. 1862 66


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