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Biomedical subjects

B Ganter

Publications and source records attributed to B Ganter.

9 recordsLinked to original sources
PubMed1999

Transcriptional activation by the myb proteins requires a specific local promoter structure.

The biological effects of the cellular c-Myb and the viral v-Myb proteins are strikingly different. While c-Myb is indispensable for normal hematopoiesis, v-Myb induces acute leukemia. The v-Myb DNA-binding domain (DBD) differs from that of c-Myb mainly by deletion of the first of three repeats which correlates with efficient oncogenic transformation and a decrease in DNA-binding activity. To investigate the difference in DNA-binding and transcriptional activation, oligonucleotide selection and electrophoretic mobility shift assays were employed. The v-Myb DBD (R2R3) shows an intrinsic DNA-binding specificity for an AT-rich downstream extension of the Myb recognition element (MRE) PyAAC(T)/(G)G for efficient binding to this site, whereas R1 within the c-Myb DBD allows for more flexibility for this downstream extension. Therefore, due to the presence of repeat R1, c-Myb can bind to a greater number of target sites. The intrinsic DNA-binding specificity of R2R3 is further supported with the results from in vivo transcriptional activation experiments which demonstrated that both the v-Myb and c-Myb DBDs require an extension of the MRE (motif #1) by a downstream T-stretch (motif #2) for full activity. Surprisingly, the T-stretch improves binding when present on either strand, but is required on a specific strand for transcriptional activation.

Animals↗
PubMed1998

D-type cyclins repress transcriptional activation by the v-Myb but not the c-Myb DNA-binding domain.

The v-Myb DNA-binding domain differs from that of c-Myb mainly by deletion of the first of three repeats. This truncation correlates with efficient oncogenic transformation and a decrease in DNA-binding activity. Here we demonstrate that the D-type cyclins, cyclin D1 and D2 in particular, specifically inhibit transcription when activated through the v-Myb DNA-binding domain, but not the c-Myb DNA-binding domain. Analysis of a cyclin D1 mutant and a dominant-negative CDK4 mutant implied that this repression is independent of complex formation with a CDK partner. Association of cyclin D1 and D2 with the Myb DNA-binding domain could be demonstrated. Increased levels of cyclin D1 and D2 resulted in a stabilization of the Myb proteins, but not in an alteration in binding of the Myb proteins to DNA. These results highlight an unexpected role for cyclin D as a CDK-independent repressor of transcriptional activation by v-Myb but not c-Myb. This differential effect of D-type cyclins on v-Myb and c-Myb might help to explain the mechanism underlying the oncogenic activity of v-Myb, which appears to be a stronger transcriptional activator following the TPA-induced differentiation of transformed monoblasts when cyclin D1 and D2 are down-regulated.

Animals↗
PubMed1997

Myb binding sites within the N-ras promoter repress transcription.

In vitro and in vivo methods were combined to determine the function of the three Myb binding sites (NrasI, NrasII and NrasIII) within the promoter region of the mouse N-ras gene. We found that the c-Myb DNA-binding domain can bind with high affinity to NrasI and NrasII, but with a reduced affinity to NrasIII. In contrast, the full length v-Myb protein from BM2 cells only bound to the middle one of the three sites, NrasII. Both c-Myb and v-Myb functioned as repressors and reduce the basal activity of the N-ras promoter by 60%, as determined by transient transfection experiments using different regions of the N-ras promoter. This repression required a functional Myb DNA-binding domain and could not be overcome by fusion to the potent VP16 activation domain. In electrophoretic mobility shift assays, the v-Myb protein is shown to be present in different conformations depending on its binding to the NrasII or the mim-1A site. The v-Myb conformation is thus suggested to play a critical role in the regulation of v-Myb activity.

Animals↗
PubMed1993

Genomic footprinting of the promoter regions of STE2 and STE3 genes in the yeast Saccharomyces cerevisiae.

Dimethyl sulfate, DNase I and micrococcal nuclease DNA cleavage were combined with the ligation-mediated polymerase chain reaction to obtain high resolution maps of the promoter regions for two cell-type-specific genes: the a-specific STE2 gene and the alpha-specific STE3 gene. We find that MCM1 binds in vivo in a-cells to a 16 bp P-box sequence located in the STE2 UAS. In alpha-cells, the footprint pattern is extended relative to a-cells, consistent with the additional binding of MAT alpha 2 to the sequences flanking each end of the P-box. A nucleosome was found adjacent to the P-box of the transcriptionally repressed a-specific STE2 UAS in alpha-cells, positioned so that the nucleosome overlaps the TATA-box. In contrast, such well-positioned nucleosomes were not found for the transcriptionally active STE2 UAS in a-cells, where instead the TATA box appears to be bound to the general transcription factor TFIID. These observations support the hypothesis that MAT alpha 2 repression of a-specific genes is mediated by nucleosomes, perhaps by exclusion of TFIID from the TATA-box.

Base Sequence↗
PubMed1992

RNA processing modulates the expression of the arcDABC operon in Pseudomonas aeruginosa.

Anaerobic growth of Pseudomonas aeruginosa on arginine depends on the arcDABC operon encoding the enzymes of the arginine deiminase pathway. The co-ordinate, anaerobic induction of these enzymes requires the FNR-like regulatory protein ANR, which activates the arc promoter lying upstream from arcD. By Northern hybridization experiments, three abundant arcA, arcAB and arcABC transcripts and three minor arcDA, arcDAB and arcDABC transcripts could be detected. The 5' ends of the arcA, arcAB and arcABC mRNAs were determined by S1 and primer extension mapping. These 5' ends appear to be generated by endonucleolytic cleavage (processing) in arcD mRNA rather than by a second promoter; this was concluded from the effects of insertion and deletion mutations in arcD. Intergenic inverted repeats between arcA and arcB as well as between arcB and arcC were shown to be involved in the formation of 3' ends of arc transcripts. Deletion of either intergenic region in the P. aeruginosa chromosome led to the loss of the arcA or arcAB transcript, respectively. Dot blot experiments revealed that arc mRNAs extracted from the wild-type strain had similar chemical half-lives in the arcA, arcB and arcC regions, ranging from 16 to 13 minutes. The half-life of arcD mRNA, by contrast, was significantly shorter, suggesting that this mRNA segment may be destabilized by the processing cuts within arcD. Deletion of the putative intergenic stem-loop structures did not result in a dramatic loss of arc mRNA stability. Thus, the intergenic hairpin structures do not contribute importantly to the overall mRNA stability; they might act primarily as partial transcription terminators and locally protect the 3' ends from exonuclease action. The expression levels of the four Arc proteins correlated approximately with the relative abundance of the corresponding mRNA segments. In conclusion, mRNA processing and, presumably, partial termination of transcription contribute to differential gene expression within the arc operon.

Amino Acid Transport Systems↗
PubMed1985

Operational evaluation of treatment for tuberculosis. Results of 8- and 12-month regimens in Peru.

To measure the effectiveness of treatment for pulmonary tuberculosis in Peru we evaluated the fate of 2,669 patients who had tuberculosis diagnosed in 1981. Two regimens were used: (1) isoniazid, rifampin, pyrazinamide, and streptomycin daily for 2 months, then either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily for 6 months; and (2) isoniazid, streptomycin, and thiacetazone daily for 2 months, then either isoniazid and streptomycin twice weekly or isoniazid and thiacetazone daily for 10 months. Patients were not assigned at random to the 2 treatment regimens; thus, the results cannot be directly compared. In the 8-month group, 70% had a favorable outcome, 14% abandoned, 9% failed, 3% died, and 3% relapsed. In the 12-month group, 53% had a favorable outcome, 34% abandoned, 6% failed, 4% died, and 2% relapsed. In patients who did not abandon treatment, the results of both regimens were nearly identical. Patients in both groups who had been treated previously had significantly lower rates of cure than those not treated previously.

Adolescent↗
PubMed1985

[Jorge Lobo's disease. Second Peruvian case].

A case of Jorge Lobo's disease is described. According to the references consulted the case presented is the second in Peru. The patient is a native of the Peruvian jungle (River Madre de Dios, State Madre de Dios). The disease was restricted to the left ear. Clinical and histopathological aspects were typical of Lobo's disease.

Adult↗
PubMed1984

Operational evaluation of treatment for tuberculosis. Results of a "standard" 12-month regimen in Peru.

To measure the operational effectiveness of treatment for tuberculosis in Peru was evaluated the outcome of a 12-month treatment regimen in 2,510 patients who had tuberculosis diagnosed in 1980. All patients had acid-fast bacilli detected by sputum microscopy and were to be treated with isoniazid, streptomycin, and thiacetazone daily for 2 months followed by either isoniazid and streptomycin twice a week or isoniazid and thiacetazone daily. Only 47% had a favorable outcome, 41% abandoned treatment, 6% failed treatment, 4% died, and 2% relapsed. Of 1,483 patients who completed treatment, 79% had a favorable outcome, whereas 21% had an unfavorable result (treatment failure, relapse, or death). These data indicate that failure to complete treatment is the major reason for the low rate of success but that, in addition, the effectiveness of the regimen in patients who complete treatment is not optimal.

Adolescent↗