Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

POU domain genes encode a family of highly conserved transacting factors that influence the transcriptional activity of several cell type-specific and ubiquitous genes. We have cloned and sequenced cDNAs encoding a novel mouse POU domain protein, Oct-11, that is closely related within the POU domain to the POU class II proteins, Oct-1 and Oct-2. Recombinant Oct-11 protein binds specifically to an octamer sequence in vitro. The Oct-11 gene is expressed during mouse embryogenesis and in the adult thymus and testis. In addition, it is abundant in the myeloma cell line P3/NS-1/1-Ag4.1. We describe the structure of Oct-11 and its chromosomal localization, and discuss the evidence that the POU class II gene family has evolved by duplication and divergence of a common ancestral gene.
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PMID:Cloning, chromosomal localization and expression pattern of the POU domain gene Oct-11. 844 7

The expression of Pax-5 gene is altered in human myeloma cells (malignant plasma cells). This altered expression is considered to be closely involved in oncogenesis of human myeloma. To investigate the possible mechanism(s) underlying this alteration, we first cloned the 1,050 bp fragment in the 5' upstream region of human Pax-5 gene by PCR-mediated gene walking method. The cloned fragment has predicted regulatory motifs for Lyf-1(Ik-1), IK-2, bHLH, E-47, Sox-5, Oct-1, GATA-1,-2, and -3, but it lacks a TATA box. By constructing deletion mutants of this fragment, its basal promoter activity was analyzed by transfecting these mutants to Cos 7 cells. The maximal promoter activity was recovered by the fragment that extends between -70 to -820 upstream of the transcription start site. Also, three DNA fragments from this cloned sequence were used as templates in gel shift assay; these fragments covered most of the predicted regulatory sites. Specific binding activities were found in each DNA fragment. Therefore, we could clone the functionally active fragment of 5' upstream region of human Pax-5 gene.
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PMID:Cloning and analysis of the human Pax-5 gene promoter. 891 52

The 5'-upstream region (1.3 kb) of the gene encoding the POU domain transcription factor Oct-1 was cloned and sequenced. CAT reporter gene analysis of this region has detected a functionally active promoter. This region contains 24 TAAT-core sites, arranged in five clusters (four to six sites in one cluster); two octamer sites (ATGCAAAT) are located in the first and second clusters; in the second one the CCAAT-box adjacent to the octamer overlaps with the TAAT-core site. As shown by gel retardation assay, Oct-1, Oct-2, and some unknown proteins from myeloma cell line NS/0 interact with the TAAT-core sites of these clusters. The results suggest autoregulation of Oct-1 gene expression that may also be controlled by other POU proteins, homeodomain proteins and CCAAT trans-action factors.
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PMID:Oct-1 promoter region contains octamer sites and TAAT motifs recognized by Oct proteins. 959 83

Analysis of the alternatively spliced isoforms of the human and mouse oct-1 genes, combined with their exon-intron structure, show a high level of evolutionary conservation between these two species. The differential expression of several oct-1 isoforms was examined by reverse transcription-polymerase chain reaction performed on the 3' region of the murine oct-1 cDNA. Variations in the relative levels and patterns of expression of the isoforms were found among different tissues. Three novel isoforms originating from the 3'-distal region of oct-1, were isolated and sequenced: Two were derived from testis, and one from myeloma cells. Splicing out of different exons as revealed in the structure of these isoforms results in reading frameshifts that presumably lead to the expression of shortened Oct-1 proteins, with distinct C-terminal tails. Altogether, six out of the eight known murine oct-1 isoforms may have distinct C-termini, implying that these multiple tails have different functional roles in cellular differentiation and physiology.
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PMID:Expression of novel alternatively spliced isoforms of the oct-1 transcription factor. 1002 87

It has been shown that pro-mRNA of transcription factor Oct-1 undergoes the tissue-specific splicing. The Oct-1L subform is synthesized in mouse lymphoid myeloma cells NS/0 of the B series and is not found in other somatic and embryonal cells. Initiation sites of oct-1R mRNA transcription are at positions -159 and -307 from the AUG codon of the oct-1R exon. In both cases, no TATA box was found in the region preceding these sites (25-30 bp). A different form of oct-1 mRNA (oct-1U) was also found in NS/0 cells, which is probably synthesized in all cell lines. This subform differs from oct-1R, in particular, by the structure of the 5T-terminal exon, which is the result of alternative splicing.
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PMID:[Tissue-specific splicing of 5'-exons of the Oct-1 transcription factor gene]. 1123 81

Transcription of the oct-1 gene is regulated by two alternative promoters: U promoter and L promoter located upstream of the exons 1U and 1L, respectively. The L promoter contains two octamer sequences of opposite orientation: proximal (ATTTGCAT) and distal (ATGCAAAT), showing high affinity toward the Oct proteins. Binding of the Oct-1 protein to the octa-sites located in the L promoter region has been confirmed in footprinting experiments. Dual luciferase assay using wild-type and mutated promoters have indicated that mutations in the proximal octa-site resulted in significant transcription enhancement both in myeloma cell line NS/0 and in fibroblast cell line 3T3 (about twofold and fivefold, respectively), whereas mutations in the distal site decreased the promoter activity (about 10% and 40%, respectively). Mutations in both octa-sites enhanced the effect and increased transcription to about fourfold in myeloma cell line NS/0 and about sixfold in fibroblast cell line 3T3. These results demonstrate that transcription of the oct-1 gene may be autoregulated by two octa-sites within the L promoter. Different function and interactive tissue-specific effect of distal and proximal octamer sequences can be suggested.
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PMID:Autoregulation of Oct-1 gene expression is mediated by two octa-sites in alternative promoter. 1671 85

Multiple myeloma (MM), a progressive hematological neoplasm, is thought to result from multiple genetic events affecting the terminal plasma cell. However, genetic aberrations related to MM are seldom reported. Using our in-house array-based comparative genomic hybridization system to locate candidate target genes with following their expression analysis, we identified POU2AF1 at 11q23.1 as a probable amplification target in MM cell lines. POU2AF1 is a B-cell-specific transcriptional co-activator, which interacts with octamer-binding transcription factors Oct-1 and Oct-2, and augments their function. Downregulation of POU2AF1 expression by specific small-interfering RNA (siRNA) inhibited MM cell growth, whereas ectopic expression of POU2AF1 promoted growth of MM cells. Among putative transcriptional targets for POU2AF1, B-cell maturation factor, TNFRSF17, enhanced its transcription by POU2AF1, and POU2AF1 directly bound to an octamer site within the 5' region of TNFRSF17. Expression level of TNFRSF17 was closely correlated with that of POU2AF1 in cell lines and primary samples of MM, and decreasing TNFRSF17 expression by means of TNFRSF17 siRNA inhibited MM cell growth. Taken together, our results suggest that POU2AF1, when activated by amplification or other mechanisms, may contribute to progression of MM by accelerating growth of MM cells through direct transactivation of one of its target genes, TNFRSF17.
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PMID:POU2AF1, an amplification target at 11q23, promotes growth of multiple myeloma cells by directly regulating expression of a B-cell maturation factor, TNFRSF17. 1762 Dec 71