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

The pX region of the human T-cell leukemia/lymphotropic virus type I (HTLV-I) contains at least four open reading frames (orfI-orfIV). orf III and orf IV encode the regulatory HTLV-I proteins Rex and Tax, which together modulate viral expression, and the p21rex protein of unknown function. By using the reverse transcriptase and polymerase chain reaction techniques on the RNA of an HTLV-I-infected cell culture, we uncovered the existence of alternatively spliced mRNAs generated through the use of three splice acceptor sites. These mRNAs encoded protein isoforms derived from the HTLV-I orf I (p12I) and orf II (p13II and p30II). An additional acceptor splice site, used in the processing of the env and tax/rex mRNAs and a singly spliced mRNA for the p21rex protein, was also identified. All of these HTLV-I mRNAs were also detected in freshly isolated cells from HTLV-I-infected individuals. Thus HTLV-I, like the human immunodeficiency virus type 1, has developed fine posttranscriptional mechanisms to increase the complexity of its genome.
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PMID:Protein isoforms encoded by the pX region of human T-cell leukemia/lymphotropic virus type I. 152 97

The vav proto-oncogene encodes a protein of unknown function that is rendered oncogenic by loss of a short N-terminal domain. A correction reported here to the vav sequence reveals that a central domain of some 230 amino acids is similar to the products of three genes: the human dbl oncogene, now known to encode a GDP-GTP exchange factor for the Ras-like polypeptide CDC42Hs; the CDC24 gene of Saccharomyces cerevisiae, which participates with CDC42Sc in organization of the cytoskeleton for budding; and the human bcr gene, which recombines with the abl oncogene in certain forms of leukemia. Furthermore, the N-terminal portion of Vav (and of CDC24) is similar to that of certain proteins that associate with filamentous structures. These similarities suggest that Vav, and perhaps also Bcr, may function as a GDP-GTP exchange factor for a Ras-like molecule such as CDC42Hs, and that its action may coordinate cytoplasmic architecture with the cell cycle. Reported evidence that the vav proto-oncogene is widely expressed in hematopoietic cells but not other cell types is extended here by detection of vav mRNA in 49 of 50 murine hematopoietic cell lines representing diverse hematopoietic lineages, and by in situ hybridization in embryos showing expression confined to the only hematopoietic tissue, fetal liver. Thus, like Dbl in other cell types, Vav may function throughout the hematopoietic compartment to govern a Ras-like signal transduction pathway.
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PMID:The hematopoietically expressed vav proto-oncogene shares homology with the dbl GDP-GTP exchange factor, the bcr gene and a yeast gene (CDC24) involved in cytoskeletal organization. 156 62

The Mov-34 mutation is a recessive embryonic lethal mutation caused by experimental introduction of a recombinant Moloney murine leukemia provirus into the mouse germline. We have cloned a full-length cDNA from the Mov-34 gene, the transcription unit disrupted by the proviral integration. This cDNA is predicted to encode a novel 321-amino acid, 36-kDa protein of unknown function. Overlapping phage lambda clones containing the entire Mov-34 gene have been isolated. The Mov-34 gene spans just over 8 kb and contains seven exons. The 5' flanking region of the Mov-34 gene contains neither "TATA" nor "CAAT" box sequences, and 5' end mapping by primer extension and ribonuclease protection reveal multiple transcription initiation sites.
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PMID:The murine Mov-34 gene: full-length cDNA and genomic organization. 183 87

The c-abl gene, originally identified as the cellular homolog of the transforming gene of the Abelson murine leukemia virus, encodes a protein-tyrosine kinase of unknown function that is expressed in all mammalian tissues. We have previously described the introduction of a mutation in the c-abl gene into the mouse germline via targeted gene disruption of embryonic stem cells. We now show that mice homozygous for this mutation are severely affected, displaying increased perinatal mortality, runtedness, and abnormal spleen, head, and eye development. We have examined components of the immune system and have found major reductions in B cell progenitors in the adult bone marrow, with less dramatic reductions in developing T cell compartments.
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PMID:Mice homozygous for the ablm1 mutation show poor viability and depletion of selected B and T cell populations. 206 53

The v-myb oncogene of avian myeloblastosis virus causes acute myelomonocytic leukemia in vivo and transforms only myeloid cells in vitro. Its product, p48v-myb, is a nuclear protein of unknown function. To determine structure-function relationships for this protein, we constructed a series of deletion mutants of v-myb, expressed them in retroviral vectors, and studied their biochemical and biological properties. We used these mutants to identify two separate domains of p48v-myb which had distinct roles in its accumulation in the cell nucleus. We showed that the viral sequences which normally encode both termini of p48v-myb were dispensible for transformation. In contrast, both copies of the highly conserved v-myb amino-terminal repeat were required for transformation. We also identified a carboxyl-terminal domain of p48v-myb which was required for the growth of v-myb-transformed myeloblasts in soft agar but not for morphological transformation.
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PMID:Structural and functional domains of the myb oncogene: requirements for nuclear transport, myeloid transformation, and colony formation. 283 3

The human T-cell leukemia virus (HTLV) types I and II are associated with specific hematological cancers. These viruses rapidly transform normal T-lymphocytes in vitro. The mechanism of HTLV-induced leukemogenesis is unknown. Structural analysis of HTLV-I and HTLV-II has revealed sequences of unknown function, termed X, at the 3' end of the proviral genome. The distal two-thirds of the X sequences are highly conserved between HTLV-I and HTLV-II. We have shown that these conserved X sequences contain a gene, termed x, that is expressed in both HTLV-I and HTLV-II by identifying a subgenomic X RNA as well as the proteins encoded by these messages. The function of this unique x gene is unknown; however, its conservation and expression suggest that it may play a role in HTLV replication and in HTLV-induced leukemogenesis.
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PMID:Human T-cell leukemia virus x gene. 299 Jun 85

The nucleotide sequence of the 3'-terminal region of the cloned bovine leukaemia virus cDNA (1474 bp) was elucidated using both Sanger and Maxam-Gilbert techniques. This DNA region contains U3 and R parts of the BLV LTR and an upstream sequence with four open reading frames (ORF) of unknown function. The comparison of the nucleotide substitutions in these ORF with the two variants of proviral BLV DNA suggests that the only pX1 ORF possesses a coding function. The role of the pX1 protein is discussed.
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PMID:[Primary structure of the 3'-terminal region of the cloned DNA of the bovine leukemia virus]. 300 63

The nucleic acid sequence of the 3' region of human T-cell leukemia virus type II (HTLV-II) proviral DNA was determined using a HTLV-II proviral clone that could be recovered as infectious, transforming virus. The sequence data indicate a region of unknown function of approximately equal to 1.6 kilobase pairs in the 3' region, analogous to the X region previously identified in human T-cell leukemia virus type I (HTLV-I). Three overlapping open reading frames are present in the X region of HTLV-II. One of these open reading frames, Xc, is most likely to encode a protein product, because it has greater predicted amino acid sequence homology (78%) with the X-IV region of HTLV-I and a greater percentage of its base differences with X-IV at the third nucleotide position of codons than do the other open reading frames. Sequences of the X-region that include the open reading frames are conserved in two deletion mutants of HTLV-II, which are associated with a subline of Mo cells with a decreased dependence on fetal bovine serum.
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PMID:Nucleotide sequence of the 3' region of an infectious human T-cell leukemia virus type II genome. 609 10

The env gene of a bovine leukemia virus (BLV) tumor-derived proviral DNA clone has been located by comparison of the translated DNA sequence with amino acid sequence data on purified gp60 and p30env (A. M. Schultz, T. D. Copeland, and S. Oroszlan (1984) Virology 135, 417-427). There is a continuous open reading frame from the N terminus of gp60 for 1446 nucleotides; gp60 is predicted to contain 268 amino acids and p30env, 214. The predicted p30env shows structural features typical of type C viral transmembrane proteins. It is also clearly related to that of the human T-cell leukemia virus (HTLV), as predicted from the DNA sequence of Seiki et al. (M. Seiki, S. Hattori, Y. Hirayama, and M. Yoshida (1983) Proc. Natl. Acad. Sci. USA 80, 3618-3622) The two proteins show 36% identities in their amino acid sequence, in an alignment requiring six gaps. More distant relatedness is also seen between BLV p30env and both murine leukemia virus p15E and Rous sarcoma virus gp36. The gp60s of BLV and HTLV are more distantly related than their p30envs, but their homology is nonetheless statistically significant. Between the presumptive terminator of the env gene and the beginning of the 3'-long terminal repeat is a region of 1817 base pairs of unknown function. Just as in the HTLV post-envelope sequence, there are at least two reading frames which are open for a significant fraction of this region. In neither the tumor-derived clone nor a clone from a virus-producing cell line, however, is there a continuous open reading frame throughout the region. Comparison of the BLV and HTLV sequences within the post-envelope region revealed a very limited but possibly significant similarity.
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PMID:The nucleotide sequence of the env gene and post-env region of bovine leukemia virus. 609 63

The AML-1/ETO fusion protein is created by the (8;21) translocation, the second most frequent chromosomal abnormality associated with acute myeloid leukemia. In the fusion protein the AML-1 runt homology domain, which is responsible for DNA binding and CBF beta interaction, is linked to ETO, a gene of unknown function. The primary sequences of the runt homology domain indicates no known DNA binding motifs, but is predicted to contain six beta-strands, two alpha-helices and a nucleotide binding motif. Mutagenesis of AML-1/ETO was performed to delimit the functional domains of the chimeric protein. Most mutations in the runt homology domain that resulted in reduced CBF beta binding also inhibited DNA binding, indicating that the DNA and CBF beta binding sequences are tightly linked. However, these activities were separated by a point mutation of residue 144, within the putative ATP binding motif, which nearly eliminated DNA binding, but did not affect CBF beta binding. Random mutagenesis identified the hydrophobic face of the amphipathic fifth beta-strand, adjacent to the putative ATP binding motif, as critical for both DNA and CBF beta binding. C-terminal deletion mutants of AML-1/ETO indicated that ETO sequences are essential for interference with AML-1B-mediated transcriptional activation, and that residue 540 defines the C-terminal boundary of a potential repression domain. Thus, these mutational analyses define the regions of AML-1/ETO which regulate its function and that may be important in promoting leukemia.
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PMID:Functional domains of the t(8;21) fusion protein, AML-1/ETO. 747 4


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