0000000000004661
AUTHOR
Ursula Kurzik-dumke
showing 16 related works from this author
Molecular partners of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, suggest its involvement in distinct cellular proces…
2018
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1. We disclose the building of hNOT/ALG3 homodimers and provide experimental evidence f…
Gene within gene configuration and expression of the Drosophila melanogaster genes lethal(2) neighbour of tid [l(2)not] and lethal(2) relative of tid…
1997
In this paper, we describe the structure and temporal expression pattern of the Drosophila melanogaster genes l(2)not and l(2)rot located at locus 59F5 vis a vis the tumor suppressor gene l(2)tid described previously and exhibiting a gene within gene configuration. The l(2)not protein coding region, 1530 nt, is divided into two exons by an intron, 2645 nt, harboring the genes l(2)rot, co-transcribed from the same DNA strand, and l(2)tid, co-transcribed from the opposite DNA strand, located vis a vis. To determine proteins encoded by the genes described in this study polyclonal rabbit antibodies (Ab), anti-Not and anti-Rot, were generated. Immunostaining of developmental Western blots with t…
Hypoxia-inducible factor 1 alpha expression increases during colorectal carcinogenesis and tumor progression
2008
Abstract Background Hypoxia-inducible factor 1 alpha (HIF-1α) is involved in processes promoting carcinogenesis of many tumors. However, its role in the development of colorectal cancer is unknown. To investigate the significance of HIF-1α during colorectal carcinogenesis and progression we examined its expression in precursor lesions constituting the conventional and serrated pathways, as well as in non-metastatic and metastatic adenocarcinomas. Methods Immunohistochemistry and Western blot is used to analyse HIF-1α expression in normal colonic mucosa, hyperplastic polyps (HPP), sessile serrated adenomas (SSA), low-grade (TA-LGD) and high-grade (TA-HGD) traditional adenomas as well as in n…
Overexpression of human homologs of the bacterial DnaJ chaperone in the synovial tissue of patients with rheumatoid arthritis
1999
Objective To study the expression of the chaperone family of J proteins in the synovial tissue of patients with rheumatoid arthritis (RA) or osteoarthritis. Methods Rabbit antibodies specific for a synthetic peptide (pHSJ1: EAYEVLSDKHKREIYD), representing the most conserved part of all J domains thus far identified—among them the Drosophila tumor suppressor Tid56—were used in immunohistochemical analyses of frozen sections of synovial tissue and immunoblotting of protein extracts of adherent synovial cells. IgG specific for Tid56 was also used. Results Both antisera predominantly and intensely stained synovial lining cells from RA patients; other cells did not stain or stained only faintly.…
Understanding Human Cancer Using Drosophila
2003
Recessive mutations of the Drosophila gene lethal(2)-tumorous imaginal discs (l(2)tid) cause neoplastic growth of the anlagen of the adult organs, the imaginal discs. Here we report that the three proteins encoded by this evolutionarily conserved gene, Tid50, Tid47, and Tid40, identified as members of the DnaJ cochaperone family, are destined for different cellular compartments, build complexes with many proteins in a developmental stage-specific manner, and are likely to be involved in different cellular processes. We show that the cytosolic Tid47 molecule is a novel component of the Hedgehog (Hh)-Patched (Ptc) signaling regulating cell/tissue polarity and spatial patterning during develop…
Loss of E-cadherin in the vicinity of necrosis in colorectal carcinomas: Association with NFκB expression
2007
The transcription factor NFkappaB regulates the expression of several tumor-related molecules associated with tumor progression and metastasis. However, the precise mechanisms by which its activation mediates these processes in diverse tumors are unknown. In this study we determined the expression of NFkappaB in various colorectal carcinoma cell lines, in a series of 90 non-metastatic and metastatic colorectal tumors and in an in vitro 3D-spheroid model of HT-29 cells simulating morphological hallmark of these adenocarcinomas, namely neoplastic glandular nests around a necrotic center. We show that the inactive cytoplasmic NFkappaB form is evidently up-regulated in the tumor epithelium, esp…
Reduced expression of TLR4 is associated with the metastatic status of human colorectal cancer.
2007
Signaling mediating colorectal cancer (CRC) progression is incompletely understood. Previously, we identified lipopolysaccharide (LPS), an endotoxin of ubiquitously existing colonic bacteria, as a pivotal stimulus increasing the metastatic potential of human CRC. Since the ubiquitous colonic bacteria release large amounts of LPS this observation could be of enormous relevance for the progression of CRC. In this study we present data contributing to the elucidation of its mode of action. Since both receptors CD14 and TLR4 act as LPS mediators, we determined their expression in various CRC cell lines and in 115 non-metastatic, lymphogenous-metastatic and haematogenous-metastatic CRC specimens…
Identification of a novel Drosophila melanogaster gene, angel, a member of a nested gene cluster at locus 59F4,5.
1996
The identification of a novel Drosophila melanogaster gene, angel, is presented in this study. angel is located on the right arm of the second chromosome at locus 59F5, close to the nested genes l(2)tid, l(2)not, l(2)rot and l(2)dtl. We describe the genetic and molecular localization of angel and present its temporal expression in the wild-type. The deduced amino acid sequence of the ANG39 protein is characterized by a nuclear localization signal. Furthermore, the central part of the predicted ANG39 protein shows significant homology to the C-terminal portion of the yeast transcriptional effector CCR4.
Genetic, cytogenetic and developmental analysis of the Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal discs (l(2)tid)
1992
Abstract Three of the twenty recessive-lethal tumor suppressor genes of Drosophila cause imaginal disc tumors in the homozygously mutated state. One of these is the lethal(2)tumorous imaginal discs (l(2)tid) gene. Histo-logical preparations show the tumorous imaginal disc epithelium to consist of a mosaic of cells in monolayer and cells in clumped arrangement. In contrast, the wild-type imaginal disc epithelium is comprised exclusively of cells in monolayer arrangement. Mutant imaginal disc tissue pieces implanted into ready-to-pupariate wild-type larvae fail to differentiate. Implantation of l(2)tid imaginal disc tissue pieces in vivo into wild-type adult flies revealed a lethal, tumorous …
Progression of colorectal cancers correlates with overexpression and loss of polarization of expression of the htid-1 tumor suppressor.
2007
Recently, we identified htid-1, the human counterpart of the Drosophila tumor suppressor gene lethal(2)tumorous imaginal discs [l(2)tid], as a direct molecular ligand of the adenomatous polyposis coli (APC) tumor suppressor. The gene encodes three cytosolic (Tid50, Tid48 and Tid46) and three mitochondrial (Tid43, Tid40 and Tid38) proteins. In the colorectal epithelium the cytosolic forms hTid50/hTid48 interact under physiological conditions with the N-terminal region of APC. This complex which associates with additional proteins such as Hsp70, Hsc70, Actin, Dvl and Axin defines a novel physiological state of APC unrelated to beta-catenin degradation. Here we show that the expression of the …
Mitochondrial localization and temporal expression of the Drosophila melanogaster DnaJ homologous tumor suppressor Tid50
1998
The Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal discs (tid) was identified as a homolog of all dnaJ-like genes known to date which have been well preserved in evolution. Homozygous D. melanogaster l(2)tid mutants l(2)tid1, l(2)tid2 and l(2)tid3 are characterized by neoplastic transformation of the adult integumental primordia, the imaginal discs, and the death at the time of puparium formation. The first part of this study is concerned with the identification and subcellular localization of the l(2)tid-encoded protein, Tid50. The second part examines its tissue specific expression during wild-type development and in tumorous imaginal discs. To specify the functi…
Sequential cleavage of the proteins encoded by HNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, results in products acting…
2017
This study provides first insights into the biosynthesis, structure, biochemistry and complex processing of the proteins encoded by hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID (NOT) and the yeast asparagine linked glycosylation 3 gene (ALG3), which encodes a mannosyltransferase. Unambiguous evidence that both the fly and human proteins act as mannosyltransferases has not been provided yet. Previously, we showed that hNOT/ALG3 encodes two alternatively spliced main transcripts, hNOT-1/ALG3-1 and hNOT-4/ALG3-4, and their 15 truncated derivatives that lack diverse sets of exons and/or carry point mutations that result in premature termination codons. Here we show that t…
Tumor suppression inDrosophila is causally related to the function of thelethal(2)tumorous imaginal discs gene, adnaJ homolog
1995
The Drosophila melanogaster tumor suppressor gene lethal(2)tumorous imaginal discs (l(2)tid) causes in homozygotes malignant growth of cells of the imaginal discs and the death of the mutant larvae at the time of puparium formation. We describe the molecular cloning of the l(2)tid+ gene and its temporal expression pattern in the wild-type and mutant alleles. Germ line rescue of the tumor phenotype was achieved with a 7.0 kb Hindlll-fragment derived from the polytene chromosome band 59F5. The l(2)tid+ gene spans approximately 2.5 kb of genomic DNA. The protein coding region, 1,696 bps long, is divided by an intron into two exons. The predicted Tid56 protein contains 518 amino acids and posse…
Sequence, molecular organization and products of the Drosophila virilis homologs of the D. melanogaster nested genes lethal(2)tumorous imaginal discs…
1997
Abstract In this study, we describe the isolation of the Drosophila virilis (Dvir) 6201-bp genomic fragment homologous to a 7047-bp genomic region of D. melanogaster (Dmel) that harbors the nested genes lethal(2)tumorous imaginal discs (l(2)tid), lethal(2)neighbour of tid (l(2)not) and lethal(2)relative of tid (l(2)rot). The isolated fragment, which maps at the cytogenetic position 50A5 on chromosome 5, carries the Dvir homologs of the Dmel genes l(2)tid and l(2)not. In both cases, the interspecific comparison of the determined sequences reveals a high homology regarding the protein coding regions and a high degree of evolutionary divergence concerning the intronic parts of the genes. In th…
Sequence of the new Drosophila melanogaster small heat-shock-related gene, lethal(2) essential for life [l(2)efl], at locus 59F4,5.
1995
Abstract In this study, we report the molecular cloning of a novel Drosophila melanogaster small heat-shock (HS)-homologous gene, l(2)efl, identified on the right arm of the second chromosome at locus 59F4,5. We describe the temporal expression of l(2)efl in the wild-type and present its structure. The deduced amino-acid sequence of the Efl protein shows significant homology to all known small HS proteins identified in Drosophila and vertebrates, and to mammalian α-crystallin.
Htid-1, the human homolog of the Drosophila melanogaster l(2)tid tumor suppressor, defines a novel physiological role of APC.
2007
Htid-1, the human counterpart of the Drosophila tumor suppressor gene lethal(2)tumorous imaginal discs (l(2)tid) encodes three splice forms translated into three cytosolic - Tid50, Tid48 and Tid46 - and three mitochondrial - Tid43, Tid40 and Tid38 - proteins. Here we provide evidence for the association of the endogenous Tid50/Tid48 proteins with the adenomatous polyposis coli (APC) tumor suppressor in normal colon epithelium, colorectal cancer cells and mouse NIH3T3 fibroblasts. Using the Glutathione S-transferase binding assay we show that the N-terminal region including the Armadillo domain (ARM) of APC is sufficient to bind the Tid molecules. Using immunoprecipitation and confocal micro…