Search PubMed⌕ Search

Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 199 records · Page 11Linked to original sources
PubMed1999

[Aspiration pneumonia caused by vertebrae of a dove in a 39 year old patient with Down syndrome].

Undetected foreign body aspiration is a well-known problem not only in children and patients with predisposing conditions like mental retardation, seizures or brain tumours, but also in healthy subjects. The clinical signs are quite different. Haemoptysis, cough, recurrent or chronic penumonia and bronchitis may occur. These symptoms are often accompanied by fever, weight loss and night sweat. Atelectasis, respiratory distress or death have been described. We demonstrate the case of a 39-year old man with Down syndrome who was transferred to our hospital because of pneumonia in the left lower lobe that had been lasting for about two months. It had been resistant to several antibiotic regimens. Computerised tomography led to the suspicion of a bronchial carcinoma with poststenotic infiltration of the lower lobe. Fibreoptic bronchoscopy and biopsy confirmed the diagnosis of a foreign body in the distal part of the left main bronchus. After two weeks of treatment with ciprofloxacin regression of the acute inflammation occurred. During a second bronchoscopy we could extract the foreign body (a 1 x 1.7 cm vertebra of a dove). It is concluded that undetected foreign body aspiration can occur in various clinical settings and fibreoptic bronchoscopy is a suitable approach providing an exact diagnosis.

Adult↗
PubMed1999

Blood-glucose self-monitoring in insulin treated type 2 diabetes mellitus a cross-sectional study with an intervention group.

Up to the present there is controversy about blood-glucose self-monitoring in type 2 diabetes. In 842 insulin-treated type 2 diabetic patients (age 60.1 +/- 10.9, diabetes duration since diagnosis 12.6 +/- 7.6 years, relative HbA1c 1.83 +/- 0.39% [relative HbA1c = HbA1c/mean normal, HPLC, Diamat]) a cross-sectional study was conducted to assess blood-glucose self-monitoring and interactions with quality of diabetes care. There was a negative correlation (r = -0.17, p < 0.001) between the frequency of blood-glucose self-tests/week and HbA1c. Performing multivariate analysis the most important parameters associated with HbA1c (R-square = 0.10) were: The frequency of blood-glucose self-tests/week (c = -0.005, p < 0.001), the insulin-dosage/kg body weight (c = 0.001, p = 0.0032) and the participation in a 5-day structured treatment and teaching programme for patients with conventional insulin therapy (5-TTP, c = 0.085, p < 0.0001). Other factors investigated in the model (age, diabetes duration, number of insulin injections/day, sex) showed no associations. Performing a sub-group analysis in patients older than 60 years (n = 396) parameters associated with HbA1c (R-square = 0.16) were the participation in a 5-TTP (c = 0.09, p = 0.002) and the frequency of blood-glucose self-tests/week (c = -0.006, p = 0.0018) too. In an further subgroup analysis patients (n = 249) were investigated who have not participated in a 5-TTP. In this cohort there were no correlations and no associations between the frequency of blood-glucose self-monitoring and HbA1c. Then, an intervention was started: 33 out of the 249 patients participated in a 5-TTP. At the time of re-examination 1 year after participating in the 5-TTP, the relative HbA1c decreased from 1.84 +/- 0.38% to 1.61 +/- 0.30% (p = 0.007) and there was a strong association between the frequency of blood-glucose self-tests/week and HbA1c (c = -0.016, p = 0.0032, R-square = 0.25). Daily blood-glucose self-monitoring was statistically associated with better quality of metabolic control. Participation in a 5-TTP and regularly blood-glucose self-monitoring is mandatory for all insulin-treated patients with type 2 diabetes mellitus.

Adult↗
PubMed1999

[Ornithosis--studies in correlation with an outbreak].

An outbreak of ornithosis with 8 cases of ornithosis pneumonia and 2 lethal complications was investigated in workers in a poultry farm and processing plant and a comparative seroepidemiological study of antigen responses was performed in 3 collectives: No. I: n = 82/87 workers in the processing plant, where the outbreak occurred; No. II: n = 83 workers in a chicken slaughter-house; No. III: n = 82 as matched-pair group to collective No. I with the same age and sex, but without occupational risk. The test systems were: genus specific complement fixation reaction (CFR), Ipazyme commercial slide kit containing LGV antigen and a type-specific microimmunofluorescence (MIF) technique with antigens binding C. psittaci, pneumonia and trachomatis IgA, IgG and IgM. 57/82 (71.9%) workers in group No. I were chlamydial antibody-positive, whereas only 22/82 of the population Nr. III--control group (odds ratio 6.2/3.2-12.3 p < or = 0.05). 16/83 (19.3%) of the workers in the chicken slaughterhouse had antibodies against chlamydia group antigens. 30/82 of the collective No. I had serological evidence of a recent or current infection with higher antibody titres in CFR and IPAZYME-Test and/or antibody response against IgA and IgM (MIF). 43.3% of the latter could be serologically detected as specific infections with C. psittaci. 10 of 18 (55%) workers employed in the recent 3 months had serological signs of an acute infection. There was no association between the point of contact with the poultry (live hang areas, slaughtery, evisceration, cooling carcasses) and the prevalence of antibody response. The possible routes of infection, inhalation of dried excretions or aerosols and via hand-to-mouth contacts are discussed. In specimens of cloacal swabs and faeces of the ducks chlamydiae could be found although the animals were asymptomatic. The results of this study demonstrate that in poultry plants, where ducks and other poultry living in an aqueous habitat are slaughtered and processed, a high risk of C. psittaci infection (70.2%) and ornithosis morbidity (25%) with a lethality of 8.3% can exist. Since the eradication of C. psittaci in poultry does not seem to be possible at the moment, preventive measures e.g. gloves, masks, information and medical examinations of the workers must be implemented in those slaughterhouses and plants where C. psittaci is suspected or common.

Abattoirs↗
PubMed1998

Tissue-specific, cell cycle-regulated chimeric transcription factors for the targeting of gene expression to tumor cells.

A major challenge in the gene therapy of proliferative diseases is the specific targeting of gene expression. Here we describe a new approach based on the development of dual-specificity promoters that are both cell type specific and cell cycle regulated. The gene of interest is driven by an artificial heterodimeric transcription factor, whose DNA-binding subunit is expressed from a tissue-specific promoter, whereas the trans-activating subunit is transcribed from a cell cycle-regulated promoter. As a result gene expression occurs preferentially in the proliferating cells of a specific type of tissue. The selectivity of this strategy is demonstrated for the expression of a transgene in proliferating melanoma cells, using a combination of cyclin A and tyrosinase promoter elements. We also show that the level of expression that can be achieved by this system is sufficient to induce a clear biological effect in a TNF-alpha cytotoxicity assay.

Animals↗
PubMed1998

Multiplex dye DNA sequencing in capillary gel electrophoresis by diode laser-based time-resolved fluorescence detection.

A new one-lane, four-dye DNA sequencing method was developed which is based on time-resolved detection and identification of fluorescently labeled primers. For fluorescent labels, we used two newly synthesized rhodamine derivatives (MR200-1, JA169), a new oxazine derivative (JA242), and a commercially available cyanine dye (CY5). The dye fluorescence was excited by a pulsed diode laser emitting at 630 nm. The fluorescence decay was detected by an avalanche photodiode using a single-filter system. The dyes used here, so-called multiplex dyes, can be distinguished and identified via their fluorescence decay patterns. The DNA fragments were labeled at the primer using linkers of various lengths and positions. For separation of the enzymatically generated DNA fragments, capillary gel electrophoresis (CGE) with a 5% linear polyacrylamide gel was employed. On covalent attachment to oligonucleotides, the dyes exhibit fluorescence decay times of 3.7 (MR200-1), 2.9 (JA169), 2.4 (JA242), and 1.6 ns (CY5) measured during CGE. The CGE mobility of the labeled DNA fragments could be controlled and nearly equalized by the coupling position and the linker length. First, time-resolved, one-lane, four-dye DNA sequencing runs in CGE are presented. The sequence information of 660 bp was determined with a probability of correct classification of > 90%. This result was obtained directly from the raw data without any of the mobility corrections that are necessary with other methods.

DNA↗
PubMed1998

The role of isochorismate hydroxymutase genes entC and menF in enterobactin and menaquinone biosynthesis in Escherichia coli.

Klebsiella pneumoniae 62-1, a triple mutant impaired in aromatic amino acid biosynthesis (Phe-, Tyr-, Trp-), excretes chorismic acid into the culture broth. When transformed with plasmids harbouring Escherichia coli genes entC or menF the mutant excretes a mixture of both chorismic and isochorismic acid indicating that not only entC but also menF encodes an isochorismate hydroxymutase (isochorismate synthase, EC 5.4.99.6) enzyme. These enzymes catalyze the first step in enterobactin or menaquinone biosynthesis, respectively. Although both gene products (EntC and MenF) catalyze the same reaction, they play distinct roles in the biosynthesis of menaquinone (MK8) and enterobactin. An E. coli mutant (PBB7) with an intact menF but a disrupted entC produced menaquinone (MK8) but no enterobactin, whereas a mutant (PBB9) with an intact entC but a disrupted menF produced enterobactin and only a trace of menaquinone (MK8). When both menF and entC were disrupted (mutant PBB8) neither menaquinone (MK8) nor enterobactin was detectable. Our previous assumption that entC is responsible for both menaquinone and enterobactin biosynthesis is inconsistent with these mutant studies and has to be revised. The presence in the promoter region of menF of a putative cAMP receptor protein binding site indicates that menF is regulated differently from entC. The menF gene was overexpressed as a fusion gene and its product (6xHis-tagged MenF) isolated. The enzyme catalyzed the formation of isochorismic from chorismic acid and as opposed to a previous publication also the reverse reaction. The enzyme was characterized and its kinetic data determined.

Chorismic Acid↗
PubMed1998

[Hepatitis B and C: current therapy].

Treatment of acute viral hepatitis B is symptomatic, fulminant cases may require liver transplantation. In chronic hepatitis B interferon (IFN)-alpha will induce sustained response rates of 30-40%. Nucleoside analogues such as famciclovir or lamivudine appear to be promising for treatment in non-responders or cirrhotic and immunosuppressed patients. IFN-alpha may reduce the rate of chronic courses in acute hepatitis C infections. Chronic hepatitis C patients with elevated ALT activities, positive serum HCV RNA and portal or bridging fibrosis on biopsy are recommended for treatment with IFN-alpha. Sustained responses are observed in less than 20% of treated patients. Retreatment with IFN-alpha may be indicated in non-responders or in case of relapse. Combination therapy of IFN-alpha plus ribavirin may emerge as treatment of choice for patients with a relapse in the near future.

Antiviral Agents↗
PubMed1998

Synthesis of reagents for the construction of hypusine and deoxyhypusine peptides and their application as peptidic antigens.

Two new synthetic methods which allow access to (2S)-deoxyhypusine, natural (2S,9R)-hypusine, (2S,9S)-hypusine, and deoxyhypusine- and hypusine-containing peptides are described. The methods involve both the construction of a deoxyhypusine reagent in which the alpha-nitrogen protecting group is orthogonal to the N-7 and N-12 protecting groups and an alternate synthesis of our previous hypusine reagent, a synthesis which provides for better stereochemical control at C-9. Synthetic hypusine and deoxyhypusine can be generated from these reagents. The hypusine-containing hexapeptide (Cys-Thr-Gly-Hpu-His-Gly) is conjugated to ovalbumin (OVA), keyhole limpet hemocyanin (KLH), and a bis-maleimide; KLH conjugates are also made with the deoxyhypusine- and lysine-containing hexapeptides. Monoclonal antibodies are generated to the hypusine-containing hexapeptide-OVA conjugate in mice. These are isolated and screened against the hypusine-containing hexapeptide-KLH and hypusine-containing hexapeptide-bis-maleimide conjugates, as well as against the deoxyhypusine-containing and lysine-containing hexapeptide-KLH conjugates. These antibodies may be useful in localizing intracellular hypusine-containing peptides as well as peptides containing hypusine analogues.

Animals↗
PubMed1998

Effect of polyamine analogues on hypusine content in JURKAT T-cells.

The availability of synthetic hypusine and deoxyhypusine has made it possible to develop analytical methods which allow for the measurement of these compounds in various tissues. The methods involve dansylation of extracts from the pellet remaining after perchloric acid precipitation of cell or tissue homogenates, followed by high-performance liquid chromatography. To demonstrate the utility of this approach, the impact of four polyamine analogues, N1,N11-diethylnorspermine (DENSPM), N1,N14-diethylhomospermine (DEHSPM), 1,6,12-triazadodecane [(4,5) triamine], and 1,7, 13-triazatridecane [(5,5) triamine], on hypusine levels in a human T-cell line (JURKAT) is evaluated. All four analogues are active in controlling cell growth and compete well with spermidine for the polyamine transport apparatus. After 144 h of exposure to JURKAT cells, DENSPM reduces putrescine to below detectable limits and spermidine to 10% of the level in control cells. The other three analogues diminish both putrescine and spermidine to below detectable limits. The effectiveness with which the compounds lower spermine levels is DENSPM > DEHSPM > (4,5) triamine > (5,5) triamine. The analogues decrease the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase in a similar fashion. Of the four polyamines, DENSPM and DEHSPM are potent at lowering intracellular hypusine levels after 144 h: 59 +/- 9% and 73 +/- 12% of control levels, respectively. The other two analogues have marginal effects.

Adenosylmethionine Decarboxylase↗
PubMed1998

Genetic complexity, structure, and characterization of highly active bovine intestinal alkaline phosphatases.

Mammalian alkaline phosphatases (APs) display 10-100-fold higher kcat values than do bacterial APs. To begin uncovering the critical residues that determine the catalytic efficiency of mammalian APs, we have compared the sequence of two bovine intestinal APs, i.e. a moderately active isozyme (bovine intestinal alkaline phosphatase, bIAP I, approximately 3,000 units/mg) previously cloned in our laboratory, and a highly active isozyme (bIAP II, approximately 8, 000 units/mg) of hitherto unknown sequence. An unprecedented level of complexity was revealed for the bovine AP family of genes during our attempts to clone the bIAP II cDNA from cow intestinal RNAs. We cloned and characterized two novel full-length IAP cDNAs (bIAP III and bIAP IV) and obtained partial sequences for three other IAP cDNAs (bIAP V, VI, and VII). Moreover, we identified and partially cloned a gene coding for a second tissue nonspecific AP (TNAP-2). However, the cDNA for bIAP II, appeared unclonable. The sequence of the entire bIAP II isozyme was determined instead by a classical protein sequencing strategy using trypsin, carboxypeptidase, and endoproteinase Lys-C, Asp-N, and Glu-C digestions, as well as cyanogen bromide cleavage and NH2-terminal sequencing. A chimeric bIAP II cDNA was then constructed by ligating wild-type and mutagenized fragments of bIAP I, III, and IV to build a cDNA encoding the identified bIAP II sequence. Expression and enzymatic characterization of the recombinant bIAP I, II, III, and IV isozymes revealed average kcat values of 1800, 5900, 4200, and 6100 s-1, respectively. Comparison of the bIAP I and bIAP II sequences identified 24 amino acid positions as likely candidates to explain differences in kcat. Site-directed mutagenesis and kinetic studies revealed that a G322D mutation in bIAP II reduced its kcat to 1300 s-1, while the converse mutation, i.e. D322G, in bIAP I increased its kcat to 5800 s-1. Other mutations in bIAP II had no effect on its kinetic properties. Our data clearly indicate that residue 322 is the major determinant of the high catalytic turnover in bovine IAPs. This residue is not directly involved in the mechanism of catalysis but is spatially sufficiently close to the active site to influence substrate positioning and hydrolysis of the phosphoenzyme complex.

Alkaline Phosphatase↗
PubMed1998

Cell cycle-independent induction of apoptosis by the anti-tumor drug Flavopiridol in endothelial cells.

The anti-tumor drug Flavopiridol is a potent inhibitor of cyclin-dependent kinases (cdks). As a consequence, Flavopiridol-treated cells arrest in both G1 and G2, but Flavopiridol has also been shown to be cytotoxic for some tumor cell lines. The underlying molecular events are, however, unclear. We now show that Flavopiridol induces apoptosis in human umbilical vein endothelial cells (HUVECs), as judged by the occurrence of classical apoptotic markers, including chromatin condensation, internucleosomal cleavage, DNA fragmentation (TUNEL assay), annexin V binding and poly(ADP-ribose) polymerase (PARP)-cleavage. Such induction of apoptosis occurs with equal efficiency in both proliferating and G0/G1-arrested cells. Because growth-arrested HUVECs lack cdk2 activity and contain high levels of the cdk inhibitor p27, our observations suggest that cell cycle regulated cdks may not be the only critical target for Flavopiridol-induced apoptosis. Surprisingly, A549 lung carcinoma cells were clearly dependent on cell proliferation for the induction of cell death, pointing to cell type-related differences in the mechanism of Flavopiridol action.

Antineoplastic Agents↗
PubMed1998

A new model of cell cycle-regulated transcription: repression of the cyclin A promoter by CDF-1 and anti-repression by E2F.

Cell cycle regulation of the cyclin A gene is determined by a bipartite repressor binding site in the region of the basal promoter, termed CDE-CHR, which also controls the expression of cell cycle genes upregulated in S or G2 (such as cdc25C). The CDE-CHR in the cyclin A promoter is recognized by both E2F complexes and CDF-1, but the contribution of each of these factors in cell cycle regulation is unknown. In the present study, we have introduced mutations into the cyclin A promoter which lead to either a loss or enhancement of E2F binding, while having only marginal effects on the interaction with CDF-1. Unlike mutants deficient for CDF-1 binding, promoter variants lacking E2F binding showed an unchanged repression in G0, thus identifying CDF-1 as the principal repressor of the cyclin A gene. The same mutants did show, however, a delayed derepression while a mutation leading to increased E2F binding resulted in premature up-regulation. These findings clearly suggest that E2F contributes to the correct timing of cyclin A transcription, presumably by acting as an anti-repressor. In agreement with this conclusion, we find that the cyclin A promoter only poorly interacts with E2F-4, which is the major E2F family member in G0 cells, while a clear binding is seen with E2F-1 and -3, which are up-regulated in late G1.

3T3 Cells↗
PubMed1998

Characterization of the microtubule-binding domain of microtubule-associated protein 1A and its effects on microtubule dynamics.

To determine how MAP1a interacts with microtubules we expressed several 6myc-tagged MAP1a fragments in P19 EC and HeLa cells. Confocal immunofluorescence microscopy showed that the fragment consisting of amino acids (aa) 1-281 of MAP1a did not bind while the fragment consisting of aa 1-630 did, indicating that the region of MAP1a between aa 281 and 630 contains a microtubule-binding domain. Deletion of the basic repeats from aa 336-540 did not result in loss of microtubule binding, suggesting that the regions flanking the basic repeats can bind MAP1a to microtubules. These observations were confirmed using an in vitro microtubule binding assay. The levels of acetylation and detyrosination of polymerized microtubules were assessed by quantitative dot blotting in cells expressing MAP1a fragments or MAP2c. Compared with untransfected cells, the polymerized tubulin in cells expressing full-length MAP1a was more acetylated and detyrosinated, but these increases were smaller than those seen in cells expressing MAP2c. Consistent with this, the microtubules in MAP2c expressing cells were more resistant to colchicine than those in cells overexpressing MAP1a. These data implicate aa 281-336 and/or 540-630 of MAP1a in microtubule binding and suggest that MAP1a is less able to stabilize microtubules than MAP2c.

Antibodies, Monoclonal↗
PubMed1998

Abrogation of c-Raf expression induces apoptosis in tumor cells.

Signal transduction pathways involving the c-Raf protein kinase are frequently activated in tumor cells. We have addressed the relevance of this activation by a loss-of-function approach. An anti-sense phosphorothioate oligonucleotide (ODN) specifically targeted against c-raf mRNA (Monia et al., 1996a) was used to block c-Raf protein expression in four different cell lines derived from lung, cervical, prostate and colon carcinomas. Concomitant with the abrogation of c-Raf expression we observed the occurrence of classical apoptotic markers, including chromatin condensation, inter-nucleosomal DNA cleavage, annexin V binding and cleavage of PARP, which was followed by cell death, affecting most of the cell population. This induction of apoptosis occurred independent of the p53 status of the cell. These findings demonstrate that c-Raf can protect tumor cells from undergoing programmed cell death, and suggest that the interference with c-Raf expression or function by ODNs or specific drugs could represent a powerful means for improving the efficacy of anti-cancer therapy.

Antineoplastic Agents↗
PubMed1998

A novel phenol hydroxylase and catechol 2,3-dioxygenase from the thermophilic Bacillus thermoleovorans strain A2: nucleotide sequence and analysis of the genes.

The new thermophilic Bacillus thermoleovorans strain A2 degrades phenol and cresols via the meta cleavage pathway. The first two enzymes involved in this process, the phenol hydroxylase and catechol 2,3-dioxygenase, encoded by the pheA and pheB genes respectively, were cloned and sequenced. The deduced amino acid sequence of pheA contains 524 amino acids with a theoretical M(r) of 59,602 Da and displays less than 10% amino acid identity to known phenol hydroxylases. The greatest amino acid identity (54%) displayed by pheA is with the larger component of the two-component 4-hydroxyphenylacetic acid hydroxylase from Escherichia coli W encoded by hpaB. No second component was present on the 3.8-kb insert. The consensus sequence GXGXXG for FAD/NAD binding sites is not present in pheA. PheB encodes a new catechol 2,3-dioxygenase of 308 amino acids (M(r) 35,487 Da) which has greatest amino acid identity (43%) with the 3-methyl catechol 2,3-dioxygenase of Pseudomonas putida UCC2 encoded by tdnC. Both pheA and pheB encode new enzymes which display low sequence homology with those previously published.

Bacillus↗
PubMed1998

Short-term effects of early-acting and multilineage hematopoietic growth factors on the repair and proliferation of irradiated pure cord blood (CB) CD34+ hematopoietic progenitor cells.

PURPOSE: Hematopoietic growth factor(s) (GF) may exert positive effects in vitro or in vivo on the survival of hematopoietic stem and progenitor cells after accidental or therapeutic total body irradiation. METHODS AND MATERIALS: We studied the clonogenic survival and DNA repair of irradiated (0.36, 0.73, and 1.46 Gy) CD34+ cord blood (CB) cells after short-term incubation (24 h) with GFs. CD34+ cells were stimulated with basic fibroblast growth factor (bFGF), stem cell factor/c-kit ligand (SCF), interleukin-3 (IL-3), IL-6, leukemia inhibitory factor (LIF), and granulocyte-monocyte colony stimulating factor (GM-CSF) alone or in combination in short-term serum-free liquid suspension cultures (LSC) immediately after irradiation and then assayed for clonogenic progenitors. DNA repair was evaluated by analysis of DNA strand breaks using the comet assay. Survival of CFU-GM, BFU-E, and CFU-Mix was determined and dose-response curves were fitted to the data. RESULTS: The radiobiological parameters (D[0] and n) showed significant GF(s) effects. Combination of IL-3 with IL-6, SCF or GM-CSF resulted in best survival for CFU-GM BFU-E and CFU-Mix, respectively. Combinations of three or more GFs did not increase the survival of clonogenic CD34+ cells compared to optimal two-factor combinations. The D[0] values for CFU-GM, BFU-E, and CFU-Mix ranged between 0.56-1.15, 0.41-2.24, and 0.56-1.29 Gy, respectively. As for controls, the curves remained strictly exponential, i.e., all survival curves were strictly exponential without any shoulder (extrapolation numbers n=1 for all tested GF(s). DNA repair capacity of CD34+ cells determined by comet assay, was measured before, immediately after irradiation, as well as 30 and 120 min after irradiation at 1 Gy. Notably, after irradiation the 2-h repair of cytokine-stimulated and unstimulated CD34+ cells was similar. CONCLUSION: Our data indicate that increased survival of irradiated CB CD34+ cells after short-term GF treatment is mediated through proliferative GF effects on the surviving fraction but not through improved DNA repair capacity.

Cell Survival↗
PubMed1998

CDF-1 mediated repression of cell cycle genes targets a specific subset of transactivators.

The cdc25C, cyclin A and cdc2 genes are regulated during the cell cycle through two contiguous repressor binding sites, the CDE and CHR, located in the region of transcription initiation and interacting with a factor termed CDF-1. The target of this repression seems to be transcriptional activation of these promoters by transcription factors bound upstream. The majority of these factors falls into the class of glutamine-rich activators, suggesting that CDF-1-mediated repression might be activation domain specific. In the present study we have used chimeric promoter constructs to demonstrate that the cdc25C UAS, but not the core promoter, is crucial for repression. In addition, we show that only specific transcription factors and activation domains are responsive to CDE-CHR-mediated cell cycle regulation. These observations clearly indicate that CDF-1 interferes with activation of transcription by a specific subset of transactivators. The repressible activation domains belong to the same class of glutamine-rich activators, pointing to specific interactions of CDF-1 with components of the transcription machinery. In agreement with this conclusion we find that a simple inversion of the CDF-CHR module completely abrogates cell cycle-regulated repression.

3T3 Cells↗