Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously we have shown that bovine vascular smooth muscle cells (SMCs) express c-myb mRNA (Reilly, C. F., Kindy, M. S., Brown, K. E., Rosenberg, R. D., and Sonenshein, G. E. (1989) J. Biol. Chem. 264, 6990-6995). Here we have characterized changes in the low level of c-myb mRNA expressed in quiescent serum-deprived subconfluent SMCs upon entry into the cell cycle. After serum stimulation, levels of c-myb mRNA increased 3-4-fold during late G1 and remained at this level during S phase. A 1.5-kilobase partial c-myb cDNA clone, isolated from a bovine SMC library, was partially sequenced and found to be 89 and 85% homologous to the human and murine c-myb genes, respectively. Using bovine and murine c-myb clones, no change in the rate of c-myb gene transcription or mRNA stability was detected during the cell cycle. Thus, the regulation of changes in c-myb mRNA levels in SMCs appears distinct from mechanisms seen in hematopoietic or fibroblastic cells. Vectors containing myb binding sites linked to the thymidine kinase promoter and the chloramphenicol acetyltransferase reporter gene were transiently transfected into SMC cultures. KHK-CAT-dAX, which contains nine concatenated myb binding sites, exhibited 7-fold more activity than the parental dAX-TK-CAT vector in exponentially growing SMCs. The levels of chloramphenicol acetyltransferase activity in exponentially growing cells were approximately 2-fold higher than in cells that had been serum deprived for 24 h and were entering quiescence. Thus SMCs produce a functional c-myb protein that can activate transcription from a heterologous promoter. Furthermore, introduction of antisense c-myb oligonucleotides to quiescent serum-deprived SMC cultures severely inhibited entry of cells into S phase upon serum addition. Thus, expression of the c-myb oncogene plays an important role in cell cycle progression of SMCs.
 ...
PMID:Expression of the c-myb proto-oncogene in bovine vascular smooth muscle cells. 153 45

We recently found that inhibition of MYB protein synthesis in human peripheral blood mononuclear cells (PBMC) exposed to human c-myb (designated MYB) antisense oligodeoxynucleotides prevents entry into S phase and cell proliferation. To determine the mechanism(s) by which down-regulation of human c-myb protein (MYB) synthesis interferes with DNA synthesis, we analyzed mRNA levels of DNA polymerase alpha and proliferating cell nuclear antigen (PCNA), transcripts of two genes required for DNA synthesis, in normal and leukemic T lymphocytes exposed to MYB antisense oligodeoxynucleotides. Expression of DNA polymerase alpha was inhibited both in normal T lymphocytes progressing from G0 to S phase and in exponentially growing CCRF-CEM leukemic cells, whereas expression of PCNA was inhibited only in mitogen-stimulated PBMC and remained essentially unaffected in the leukemia T-cell line. The functional link between expression of MYB and DNA polymerase alpha mRNAs was further demonstrated by analyzing DNA polymerase alpha mRNA levels in a temperature-sensitive (ts) fibroblast cell line (TK-ts13; TK is thymidine kinase) constitutively expressing human MYB mRNA driven by the simian virus 40 (SV40) promoter. In the MYB-expressing TK-ts13 cells, DNA polymerase alpha mRNA levels were unaffected following shift to the nonpermissive temperature of 39.6 degrees C, whereas in the parental line, DNA polymerase alpha mRNA levels were readily down-regulated. These findings indicate that the expression of MYB is related to that of DNA polymerase alpha in cells expressing MYB at high levels and suggest that there is a functional link between c-myb and DNA polymerase alpha mRNA expression during cell cycle progression of normal T lymphocytes.
 ...
PMID:Inhibition of T-cell proliferation by a MYB antisense oligomer is accompanied by selective down-regulation of DNA polymerase alpha expression. 169 13

The B-myb cDNA has extensive sequence similarities to the c-myb proto-oncogene, but, at variance with c-myb, it is expressed in cells other than hematopoietic cells. In this paper, we show that (1) B-myb is expressed in mouse, human, and hamster fibroblasts; (2) B-myb mRNA levels are growth-regulated in both fibroblasts and peripheral blood mononuclear cells; (3) by its mode of growth regulation (peak of expression, behavior in G1-specific temperature sensitive (ts) mutants and in the presence of cycloheximide), B-myb can be classified, like c-myb, thymidine kinase, PCNA, and others, as a late growth-regulated gene; (4) B-myb mRNA levels decrease when HL-60 cells are induced to differentiate; and (5) the increase in mRNA levels in serum-stimulated cells is only partially explained by an increase in rate of transcription. The possibility that the B-myb gene may be the equivalent in fibroblasts and epithelial cells of the c-myb proto-oncogene of hematopoietic cells is discussed.
 ...
PMID:Growth regulated expression of B-myb in fibroblasts and hematopoietic cells. 171 94

The nuclear proto-oncogene c-myb is preferentially expressed in lymphohematopoietic cells, in which it plays an important role in the processes of differentiation and proliferation. The mechanism(s) that regulates c-myb expression is not fully understood, although in mouse cells a regulatory mechanism involves a transcriptional block in the first intron. To analyze the contribution of the 5' flanking sequences in regulating the expression of the human c-myb gene, we isolated a genomic clone containing extensive 5' flanking sequences, the first exon, and a large portion of the first intron. Sequence analysis of a subcloned 1.3-kb BamHI insert corresponding to 687 nucleotides of the 5' flanking sequence, the entire first exon, and 300 nucleotides of the first intron revealed the presence of closely spaced putative Myb binding sites within a segment extending from nucleotides -616 to -575 upstream from the cap site. A 165-bp segment containing these putative Myb binding sites was linked to a human thymidine kinase (TK) cDNA driven by a low-activity proliferating cell nuclear antigen promoter and cotransfected into TK- ts13 cells with a plasmid in which a full-length human c-myb cDNA is driven by the early simian virus 40 promoter; Myb inducibility of TK mRNA expression was observed both in transient expression assays and in stable transformants. The highest level of inducibility was detected when the 165-bp fragment was placed 138 bp upstream of the proliferating cell nuclear antigen promoter-TK cDNA reporter unit or 3' of the TK cDNA. Mutation of the putative Myb binding sites greatly reduced c-myb transactivation of TK mRNA expression and specifically reduced the binding of in vitro-translated Myb protein at those sites. Finally, c-myb transactivated TK mRNA expression driven by a segment of the authentic c-myb 5' flanking region containing the Myb binding sites. These data suggest that human c-myb maintains high levels of Myb protein in cells that require this gene product for proliferation and/or differentiation by an autoregulatory mechanism involving Myb binding sites in the 5' flanking region.
 ...
PMID:Positive autoregulation of c-myb expression via Myb binding sites in the 5' flanking region of the human c-myb gene. 194 82

The hemopoietic growth factor interleukin 3 (IL-3) supports the survival and proliferation of multipotent and committed progenitor cells in vitro. To elucidate the molecular mechanisms triggered by IL-3 we studied the expression of cell cycle-related genes in a recently established human IL-3-dependent clone (M-07e). No changes in the level of expression of early (c-myc), mid (ornithine decarboxylase), or mid-late G1 (p53, c-myb) cell cycle genes were detected after restoration of IL-3 in deprived cells. The fact that only late G1-S-phase genes [proliferating cell nuclear antigen (PCNA) thymidine kinase (TK), histone H3] are modulated by IL-3 suggests that this factor may control human cell proliferation by acting at the G1-S boundary.
 ...
PMID:Interleukin 3-dependent proliferation of the human Mo-7e cell line is supported by discrete activation of late G1 genes. 199 64

We have examined the expression of 13 proto-oncogenes in proliferating and terminally differentiated cardiac and skeletal muscle. Total RNA was prepared from intact ventricular cardiac-muscle tissue and from purified ventricular cardiac-muscle cells of neonatal and adult rats and from cultured proliferating and terminally differentiated L6A1 rat skeletal-muscle cells. cDNA probes for histone H4, thymidine kinase, myosin heavy chain and M-creatine kinase were used to assess cellular proliferation and differentiation. Oncogenes c-myc, c-raf, c-erb-A, c-ras-H, c-ski, and c-sis were expressed in both proliferating and differentiated cardiac muscle tissue and cells, whereas c-myb expression was not observed in either. c-src was expressed only in neonatal cardiac muscle tissue and cells. c-fms, c-abl, and c-ras-K were expressed in tissue from both neonatal and adult animals but only in purified cells from neonatal animals. c-fes/fps was expressed only in neonatal cardiac muscles cells. c-fos expression was not observed in cardiac-muscle tissue from either neonatal or adult rats, but surprisingly was abundantly expressed in freshly isolated cardiac-muscle cells from animals of both ages. These results emphasize that biochemical analysis using intact cardiac-muscle tissue may not necessarily reflect muscle-specific cell processes. They also show that the expression of c-fos can be activated by the cell isolation procedure. c-myc, c-ski, c-ras-H, c-ras-K, c-abl, c-raf and c-erb-A were expressed in both proliferating and terminally differentiated skeletal-muscle cells, whereas c-myb, c-fos, c-src and c-fms transcripts were observed only in proliferating cells. c-fes/fps and c-sis were not expressed in dividing or fused skeletal-muscle cells. These results demonstrate unique tissue and cell-specific patterns of proto-oncogene expression and suggest that these genes may be involved with the regulation of cellular proliferation and terminal differentiation in striated muscle.
 ...
PMID:Proto-oncogene expression in proliferating and differentiating cardiac and skeletal muscle. 244 74