Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new human plasma cell line, UMJF-2, has been derived from the bone marrow of a patient with multiple myeloma. Morphological studies disclosed large nucleoli, moderate numbers of mitochondria, and scant endoplasmic reticulum consistent with a plasmablastic morphology. The cells have immunologic characteristics of early plasma cells, including intense expression of cytoplasmic IgG-lambda and weaker, but discernible, expression of surface IgG-lambda. Cell surface antigens defined by the monoclonal antibodies OKT10 (CD38) and PCA-1, characteristic of mature plasma cells, and B1 (CD20), B4 (CD19), and I-2 (HLA-DR), characteristic of earlier stages of B-lymphocyte differentiation, are present on UMJF-2 cells. Cytogenetic studies reveal the presence of trisomy 12. UMJF-2 does not contain the Epstein-Barr virus by Southern blot analysis. Tissue culture media conditioned by these cells contains a soluble immunosuppressive factor, capable of inhibiting pokeweed mitogen induced IgM secretion by normal human B-lymphocytes. UMJF-2 provides a model for the study of the pathogenesis of polyclonal hypogammaglobulinemia in human multiple myeloma.
Leukemia 1991 Jul
PMID:Characterization of a new human multiple myeloma cell line, UMJF-2, which suppresses antibody production by B-lymphocytes in vitro. 164 57

Cytoplasmic inclusions of great complexity are encountered in an undifferentiated sarcoma of a 67-year-old woman. The tumor arising in adipose tissue between muscles of the parspinous musculature contains inclusions in most tumor cells represented by four different morphologic types. Two are intracisternal, designated microtubular reticular structure (TRS) and tubular confronting cisternae (TCC). Two others are cytoplasmic and consist of crystalline microtubular arrays and of confronting cisternal complexes of smooth endoplasmic reticulum (SER). This latter is uniquely complex and not found in previous descriptions. Tumors of mesenchymal origin and experimental virus-induced tumors are known to contain short segments of confronting cisternae and TRS. Tubuloreticular structures and TCC are well documented in cases of lupus, in human immunodeficiency virus infections, in T-cell leukemia, and in experimental viral hepatitis in chimpanzees. The patient presented has none of the coincidental pathologic condition associated with occurrence of TRS and TCC. The morphology of the inclusions and their relationships are illustrated although their biological significance remains obscure.
 ...
PMID:Soft tissue sarcoma with complex membranous and microtubular inclusions. 166 96

The mitogenic membrane glycoprotein (gp55) encoded by Friend erythroleukemia virus is inefficiently processed from the rough endoplasmic reticulum (RER) and only 3-5% reaches plasma membranes. Because this processed component (gp55P) contains larger and more complex oligosaccharides, it can be separated from RER gp55. In nonreducing conditions, gp55P is a unique disulfide-bonded dimer, whereas RER gp55 consists of monomers and dimers with diverse intrachain and interchain disulfide bonds. This suggests that gp55 folds heterogeneously and that only one homodimer is competent for export from the RER. Pulse-chase analyses of gp55 components labeled with radioactive amino acids indicated that formation of diverse disulfide-bonded components occurred within minutes of polypeptide synthesis and that malfolded components did not later isomerize to generate dimers competent for export from the RER. Chemical studies suggested that all 12 cysteines of gp55 were oxidized within 5 min after synthesis of the protein. In contrast, the envelope glycoprotein precursor (gPr90) encoded by a replication-competent murine leukemia virus folds more homogeneously, and it is then processed and cleaved to form an extracellular glycoprotein gp70 plus a transmembrane protein p15E. The fully processed glycoprotein contains an unoxidized cysteine sulfhydryl that isomerizes reversibly with a disulfide bond that links gp70 to p15E. Consequently, only a proportion of gp70 and p15E is disulfide-bonded, and dissociation occurs when the environment becomes even slightly reducing. The gp55 glycoprotein appears to be an extreme example of protein malfolding associated with imprecise and irreversible disulfide bonding. We discuss evidence that folding inefficiencies are common for retroviral proteins that have newly evolving pathogenic functions.
 ...
PMID:Disulfide bonding controls the processing of retroviral envelope glycoproteins. 174 94

This paper documents the effects of brefeldin A (BFA) on the processing and transport of viral envelope glycoproteins in a retrovirus-transformed murine erythroleukemia (MEL) cell line. BFA is a fungal metabolite that disrupts intracellular membrane traffic at the endoplasmic reticulum (ER)-Golgi complex junction. In MEL cells, BFA inhibited the processing of the newly synthesized precursor, gPr90env, of the murine leukemia virus envelope protein, gp70, and curtailed the budding of virions into the culture medium by blocking the transport of this protein out of the ER. The block resulted in the intracellular accumulation of gPr90env and two putative products of its processing (78 and 66 kDa). The results of endoglycosidase (endo) H and D digestion of the viral glycoproteins in the presence and absence of BFA indicated that (i) there was no glycoprotein processing during the first approximately 2 h of the BFA block; (ii) active Golgi enzymes relocated to the ER in approximately 2 h during BFA treatment, resulting in the production of partially endo H-resistant forms of the spleen focus-forming virus glycoprotein, gp55 (in controls, this glycoprotein was generally retained in the ER as an endo H-sensitive entity); and (iii) proteolytic processing of gPr90env to gp70 occurred prior to the acquisition of endo H resistance and at approximately the same time as endo D sensitivity (i.e. in a cis Golgi compartment). In control cells, the spleen focus-forming virus glycoprotein, gp55, underwent turnover with a half-life of approximately 5 h. In contrast, its turnover was considerably slower during BFA treatment (t 1/2 = approximately 20 h), suggesting that transport of gp55 out of the ER was required for its degradation or that BFA afforded it protection from proteolysis within the ER.
 ...
PMID:Effects of brefeldin A on the processing of viral envelope glycoproteins in murine erythroleukemia cells. 185 Nov 69

The roles played by the N-linked glycans of the Friend murine leukemia virus envelope proteins were investigated by site-specific mutagenesis. The surface protein gp70 has eight potential attachment sites for N-linked glycan; each signal asparagine was converted to aspartate, and mutant viruses were tested for the ability to grow in NIH 3T3 fibroblasts. Seven of the mutations did not affect virus infectivity, whereas mutation of the fourth glycosylation signal from the amino terminus (gs4) resulted in a noninfectious phenotype. Characterization of mutant gene products by radioimmunoprecipitation confirmed that glycosylation occurs at all eight consensus signals in gp70 and that gs2 carries an endoglycosidase H-sensitive glycan. Elimination of gs2 did not cause retention of an endoglycosidase H-sensitive glycan at a different site, demonstrating that this structure does not play an essential role in envelope protein function. The gs3- mutation affected a second posttranslational modification of unknown type, which was manifested as production of gp70 that remained smaller than wild-type gp70 after removal of all N-linked glycans by peptide N-glycosidase F. The gs4- mutation decreased processing of gPr80 to gPr90, completely inhibited proteolytic processing of gPr90 to gp70 and Pr15(E), and prevented incorporation of envelope products into virus particles. Brefeldin A-induced mixing of the endoplasmic reticulum and parts of the Golgi apparatus allowed proteolytic processing of wild-type gPr90 to occur in the absence of protein transport, but it did not overcome the cleavage defect of the gs4- precursor, indicating that gs4- gPr90 is resistant to the processing protease. The work reported here demonstrates that the gs4 region is important for env precursor processing and suggests that gs4 may be a critical target in the disruption of murine leukemia virus env product processing by inhibitors of N-linked glycosylation.
 ...
PMID:Mutational analysis of N-linked glycosylation sites of Friend murine leukemia virus envelope protein. 189 86

Retrovirus entry into cells is mediated by specific binding of the envelope glycoprotein to a cell membrane receptor. Constitutive envelope gene expression prevents infection by interfering with the binding of viruses which recognize the same receptor. We have used this property to investigate the receptor binding capacities of deleted or truncated murine leukemia virus ecotropic envelope glycoproteins. Friend murine leukemia virus envelope glycoproteins bearing internal amino-terminal deletions, or a soluble 245-amino-acid gp70 amino-terminal fragment, were expressed in NIH 3T3 cells. The susceptibility of these cells to ecotropic and amphotropic virus infection was determined. We observed that both membrane-bound and soluble forms of the gp70 245-amino-acid amino-terminal domain induced resistance to ecotropic virus, indicating that this fragment binds the ecotropic receptor. Binding occurs both at the cell surface and in the endoplasmic reticulum, as shown by the use of soluble envelope fragments either secreted in the culture supernatants or retained in the endoplasmic reticulum lumen by a KDEL sequence. These results suggest that the gp70 amino-terminal domain folds into a structure which recognizes the ecotropic receptor regardless of the carboxy-terminal part of the molecule.
 ...
PMID:An amino-terminal fragment of the Friend murine leukemia virus envelope glycoprotein binds the ecotropic receptor. 207 45

A total of 3430 polypeptides (2592 cellular; 838 secreted) from transformed human amnion cells (AMA) labeled with [35S]methionine were separated and recorded using computer-aided two-dimensional (2-D) gel electrophoresis. A master 2-D gel database of cellular protein information that includes both qualitative and quantitative annotations has been established. The protein numbers in this database differ from those reported in an earlier version (Celis et al. Leukemia 1988, 2,561-602) as a result of changes in the scanning hardware. The reported information includes: percentage of total radioactivity recovered from the gels (based on quantitations of polypeptides labeled with a mixture of 16 14C-amino acids), protein name (including credit to investigators that aided identification), antibody against protein, cellular localization, (nuclear, 40S hnRNP, 20S snRNP U5, proteasomes, endoplasmic reticulum, mitochondria, Golgi, ribosomes, intermediate filaments, microfilaments and microtubules), levels in fetal human tissues, partial protein sequences (containing information on 48 human proteins microsequenced so far), cell cycle-regulated proteins, proteins sensitive to interferons alpha, beta, and gamma, heat shock proteins, annexins and phosphorylated proteins. The results presented should be considered as the initial phase of a joint effort between our laboratories to undertake a general and systematic analysis of human proteins. Using this integrated approach it will be possible to identify phenotype-specific proteins, to microsequence them and store the information in the database, to identify the corresponding genes, to search for homology with previously characterized proteins and to study the function of groups of proteins (pathways, organelles, etc.) that exhibit interesting regulatory properties. In particular, the 2-D gel protein database may become increasingly important in view of the concerted effort to map and sequence the entire human genome.
 ...
PMID:Comprehensive two-dimensional gel protein databases offer a global approach to the analysis of human cells: the transformed amnion cells (AMA) master database and its link to genome DNA sequence data. 209 Apr 60

We studied the expression of beta-galactosidase (beta-gal) and 15 gag-beta-gal fusion proteins in the presence of Moloney murine leukemia virus wild-type core (gag) proteins. Analysis indicated that proteins retaining the amino-terminal portion of gag through the capsid protein-coding region were incorporated into retrovirus particles. Proteins which deleted portions of the capsid protein were assembled into virions at low efficiency, indicating the importance of capsid protein interactions in retrovirus assembly. Fusion proteins which retained the amino-terminal matrix protein of the gag polyprotein but which lacked the capsid protein were released efficiently from cells in a nonviral form. The nonviral form was characterized by a high sedimentation coefficient and a low density, suggestive of membrane vesicles. While beta-gal was present in the cytoplasm of expressing cells, all fusion constructs were associated with cellular membranes. gag-beta-gal proteins which were capable of release from cells demonstrated a two-component immunofluorescence staining pattern consisting of a circle of fluorescence around the nucleus and a punctate pattern of staining throughout the remainder of the cell. Interestingly, fusions within the matrix protein were trapped intracellularly and yielded distinct perinuclear staining patterns, possibly localizing to the rough endoplasmic reticulum and/or Golgi. This observation suggests that Moloney murine leukemia virus gag proteins travel to the plasma membrane by vesicular transport associated with the cytoplasmic face of intracellular vesicles.
 ...
PMID:Assembly of gag-beta-galactosidase proteins into retrovirus particles. 210 1

Glycoproteins from the human T leukemia cells Jurkat were found to bind to the GalNAc alpha 1----Ser/Thr-specific lectin from Salvia sclarea seeds. The analysis of the O-linked saccharides of immunopurified leukosialin, the major [3H]glucosamine-labeled glycoprotein in Jurkat cell lysate, revealed the presence of mainly GalNAc alpha 1----Ser/Thr with only minor amounts (approximately 17%) of more complex O-glycans. A comparison between Jurkat and K562 cell glycosyltransferase involved in the biosynthesis of O-linked carbohydrates showed that a markedly lower activity of UDP-Gal:GalNAc alpha 1----Ser/Thr beta 1----3galactosyltransferase is apparently responsible for the presence of truncated O-glycans in the Jurkat cell line. The O-glycosylation defect makes Jurkat cells an ideal model to study the initiation of O-linked saccharides. Pulse-chase experiments with [35S] methionine showed that the addition of GalNAc to leukosialin is responsible for the decreased mobility of the mature glycoprotein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Furthermore, no biosynthetic intermediates between the O-glycan-free precursor and the fully O-glycosylated form could be detected either with an anti-leukosialin antiserum or with the GalNAc-specific lectin. Lowering the chase temperature to 15 degrees C completely inhibited the transfer of GalNAc to the peptide core indicating that O-glycan initiation takes place in the first Golgi elements and not in transitional vesicles between endoplasmic reticulum and Golgi. In addition, treatment of the cells with monensin did not inhibit GalNAc transfer to leukosialin apoprotein. These results indicate that the initiation of O-glycosylation in Jurkat cells starts in the cis-Golgi stacks.
 ...
PMID:Biosynthesis of truncated O-glycans in the T cell line Jurkat. Localization of O-glycan initiation. 214 May 70

Friend spleen focus-forming virus (SFFV) is a defective murine C-type retrovirus which causes a multi-stage erythroleukaemia in mice and erythroblastosis in bone marrow cultures. The SFFV env gene encodes a membrane glycoprotein, gp55, which is located on the cell surface and in the rough endoplasmic reticulum and is essential both for the induction of leukaemia in vivo and erythroblast proliferation in vitro. The mechanism by which gp55 causes increased erythroblastosis and ultimately leukaemia is unknown, but a reasonable suggestion is that gp55 can mimic the action of erythropoietin by binding to its receptor (Epo-R), thereby triggering prolonged proliferation of erythroid cells. To test this possibility, we have co-expressed gp55 and the murine Epo-R in a fibroblast cell line. We show here that in such cells, the SFFV glycoprotein binds directly to Epo-R. Furthermore, when an interleukin-3 (IL-3)-dependent lymphoid cell line was co-infected by SFFV and a virus that carries the Epo-R gene, it could grow without IL-3. We suggest that through direct binding to Epo-R, gp55 can stimulate the receptor and by-pass the normal requirement for Epo, causing prolonged proliferation of infected erythroid cells. This could be the first step of leukaemogenesis induced by Friend virus.
 ...
PMID:Activation of cell growth by binding of Friend spleen focus-forming virus gp55 glycoprotein to the erythropoietin receptor. 215 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>