RESUMEN
BACKGROUND: Physiological function of cyclin-dependent kinase 12 (CDK12) is crucial for several cellular processes, including regulation of transcription, RNA splicing, transcription termination and polyadenylation. It is well documented by now that CDK12 controls transcription of the unique set of genes involved in DNA-damage response, replication of DNA and response to cellular stress. Just recently, a key function of CDK12 in the induction of tandem duplication of specific DNA sequences within the metastatic castrate resistant prostate tumors has been documented. Therefore, it is possible to recognize CDK12 as a tumor suppressor; nevertheless, there is a growing body of evidence that CDK12 can support tumor growth under specific circumstances and thus act as a tumor oncogene. CDK12 therefore represents an alternative dia-gnostic approach for breast, ovarian and prostate tumors, especially when conventional treatment is not active and there is a need for more effective approaches, such as concept of synthetic lethality. METHODS: The discussed scientific papers can be reached at the PubMed and Scopus databases before 1th of April 2020. PURPOSE: The aim of the review is to summarize current knowledge relevant to the function of CDK12 as a tumor suppressor or oncogene in various tumors and to discuss the use of specific CDK12 inhibitors for patient treatment. At the end of the article, we discuss the potential use of CDK12 in the treatment of specific tumors by its targeted inhibition in monotherapy or in combination with poly (ADP ribose) polymerase 1 (PARP1) and checkpoint kinase 1 (CHK1) inhibitors. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Asunto(s)
Quinasas Ciclina-Dependientes/metabolismo , Genes Supresores de Tumor , Terapia Molecular Dirigida , Neoplasias/patología , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismoRESUMEN
Several members of the TGF-beta family are known to effectively regulate the fate of hematopoietic progenitor cells in a complex and context-dependent manner. Growth differentiation factor-15 (GDF15) is a divergent member of the TGF-beta family. This stress-induced cytokine has been proposed to possess immunomodulatory functions and its high expression is often associated with progression of a variety of pathological conditions. GDF15 is also induced by chemotherapy and irradiation. Very few fundamental studies have been published regarding the effect of GDF15 in hematopoiesis. In this study, we analyzed the hematological status of untreated and gamma-irradiated mice deficient for GDF15 as a result of genetic knock-out (KO), in order to clarify the regulatory role of GDF15 in hematopoiesis. Significant differences between GDF15 KO mice and their pertinent WT controls were found in the parameters of blood monocyte numbers, blood platelet size, and distribution width, as well as in the values of bone marrow granulocyte/macrophage progenitor cells. Different tendencies of some hematological parameters in the GDF15 KO mice in normal conditions and those under exposure of the mice to ionizing radiation were registered. These findings are discussed in the context of the GDF15 gene function and its lack under conditions of radiation-induced damage.
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Rayos gamma/efectos adversos , Factor 15 de Diferenciación de Crecimiento/deficiencia , Factor 15 de Diferenciación de Crecimiento/efectos de la radiación , Hematopoyesis/efectos de la radiación , Animales , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/efectos de la radiación , Femenino , Hematopoyesis/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
The beta-N-methylamino-l-alanine (BMAA) is a non-proteinogenic amino acid discussed to be produced by cyanobacteria forming harmful blooms. Since BMAA is suspected etiological agent in neurodegenerative diseases, there is a need to study and validate whether and in what concentrations can BMAA be present in human tissues. The aim of the present study was to validate analytical and extraction procedures for quantification of non-derivatized BMAA in the urine using liquid chromatography and commercial ELISA Kit. The study was focused on BMAA in different forms - dissolved, protein associated and total. The validated protocol included SPE followed by HILIC MS/MS for analyses of non-derivatized free form of BMAA with a limit of quantification 20 ng/mL. The methods for other BMAA forms (i.e. protein-associated and total) were also assessed but high matrix interferences did not allow their implementation. The method was used for analyses of free BMAA in 23 urine samples from healthy volunteers and psychiatric patients suffering from nonspecific neurological symptoms. Traces of BMAA were suspectedly detected in a single urine sample but they were not unequivocally proved according to all conservative analytical criteria. BMAA was also not confirmed in a repeatedly collected sample from the same person. The evaluated commercial BMAA ELISA Kit (Abraxis) was not suitable for determination of BMAA in extracted urine samples because of systematically highly false positive results. In agreement with recent findings, analyses of BMAA appear to methodologically challenging, and further research on BMAA in human tissues (or its precursors with potency to form BMAA under natural conditions or - eventually - during sample processing) is needed to clarify its potential ethiological role in neurodegenerative diseases.
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Aminoácidos Diaminos/orina , Trastornos Mentales/orina , Neurotoxinas/orina , Adulto , Anciano , Cromatografía Liquida/métodos , Toxinas de Cianobacterias , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Espectrometría de Masas en Tándem/métodosRESUMEN
Isoflavones are natural phytoestrogens with antioxidant and endocrine-disrupting potencies. Monitoring of their levels is important to ensure the high quality and safety of food, milk, and dairy products. The efficiency and accuracy of phytoestrogen analyses in complex matrices such as milk depend on the extraction procedure, which often uses hydrolysis by means of the ß-glucuronidase/sulfatase enzyme originating from Helix pomatia. The present study reveals that the commercially available hydrolytic enzyme is contaminated by several phytoestrogen isoflavones (genistein, daidzein, formononetin, and biochanin A) and their metabolite equol, as well as flavones (naringenin and apigenin) and coumestrol. We show that the concentrations of daidzein and genistein in the enzyme could have impaired the results of analyses of the main isoflavones in several previously published studies. Of 8 analyzed compounds, only equol was confirmed in the present study and it serves as a reliable marker of phytoestrogens originating from cow feed. Critical reassessment of phytoestrogen concentrations in milk is needed because several previously published studies might have overestimated the concentrations depending on the extraction procedure used.
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Leche/química , Fitoestrógenos , Animales , Bovinos , Cumestrol , Femenino , Glucuronidasa , Isoflavonas , ÓvuloRESUMEN
Cyclin-dependent kinases (CDKs) participate in many cellular processes and play a crucial role in the regulation of cell cycle and transcription processes. Recently, CDK12 was identified as a key factor orchestrating transcription of genes, such as BRCA1, ATM, ATR, FANCI and FANCD2, which are involved in the DNA-damage response pathway. Importantly, inhibition of function of these genes commonly leads to induction of genomic instability followed by cancer development, but the precise contribution of CDK12 to these processes is to be unveiled. Nevertheless, several mutations affecting function of CDK12 were already identified in a variety of tumors of different origin (ovary, breast, prostate, intestine) making tumors sensitive to cytostatics promot-ing DNA damage (platin derivatives, alkylating regimens) and inhibitors of DNA repair (PARP inhibitors). Such an effect has been already observed in the model of high grade serous ovarian carcinomas. Thus, CDK12 is becoming a potential therapeutic target of drugs causing synthetic lethality in these cells. Our review summarizes most recent information about CDK12 function in cancer and discusses potential use of CDK12 in clinics.
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Carcinogénesis , Quinasas Ciclina-Dependientes/fisiología , Daño del ADN , Reparación del ADN , Transcripción Genética , Antineoplásicos/uso terapéutico , Antineoplásicos Alquilantes/uso terapéutico , Carcinogénesis/genética , Inestabilidad Cromosómica , Cisplatino/uso terapéutico , Quinasas Ciclina-Dependientes/genética , Femenino , Humanos , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
The paper presents the development of an advanced extraction and fast analytical LC MS/MS method for simultaneous analyses of reduced and oxidized glutathione (GSH and GSSG, respectively) in different animal tissues. The simultaneous determination of GSH and GSSG is crucial because the amount and ratio of both GSH and GSSG may be altered in response to oxidative stress, an important mechanism of toxicity. The method uses the derivatization of free thiol groups in GSH. Its performance was demonstrated for less explored tissues (lung, brain, and liver) in mouse. The combined extraction and analytical method has very low variability and good reproducibility, maximum coefficients of variance for within-run and between-run analyses under 8 %, and low limits of quantification; for GSH and GSSG, these were 0.2 nM (0.06 ng/mL) and 10 nM (6 ng/mL), respectively. The performance of the method was further demonstrated in a model experiment addressing changes in GSH and GSSG concentrations in lung of mice exposed to CdO nanoparticles during acute 72 h and chronic 13-week exposures. Inhalation exposure led to increased GSH concentrations in lung. GSSG levels were in general not affected; nonsignificant suppression occurred only after the longer 13-week period of exposure. The developed method for the sensitive detection of both GSH and GSSG in very low tissue mass enables these parameters to be studied in cases where only a little sample is available, i.e. in small organisms or in small amounts of tissue.
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Cadmio/toxicidad , Cromatografía Liquida/métodos , Disulfuro de Glutatión/análisis , Glutatión/análisis , Exposición por Inhalación/análisis , Hígado/química , Pulmón/química , Espectrometría de Masas/métodos , Animales , Cadmio/metabolismo , Femenino , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Ratones , Ratones Endogámicos ICR , Nanopartículas/metabolismo , Nanopartículas/toxicidadRESUMEN
Despite intensive research into toxic bloom-forming cyanobacteria, the majority of their metabolites remain unknown. The present study explored in detail a novel bioactivity identified in cyanobacteria, i.e. inhibition of gap junctional intercellular communication (GJIC), a marker of tumor promotion. The extracellular mixture (exudate) of the cyanobacterial strain Cylindrospermopsis raciborskii (SAG 1.97) was fractionated by semi-preparative reversed phase HPLC, and the fractions assessed for their potencies to inhibit GJIC. Two non-polar fractions that significantly inhibited GJIC were further fractionated, tested and analyzed using multiple mass spectrometric methods. Investigations led to the identification of a putative chemical compound (molecular formula C18H34O3, m/z 299.2581 for the [M+H](+) ion) responsible for observed bioactivities. Specific inhibitors of signaling pathways were used to screen for biochemical mechanisms beyond GJIC inhibition, and the results indicate the involvement of ERK1/2 kinases via a mechanism related to the action of epidermal growth factor EGF but clearly distinct from other anthropogenic tumor promoters like polychlorinated biphenyls or polycyclic aromatic hydrocarbons. The chemical and in vitro toxicological characterizations of the newly described metabolite provide important insights into the still poorly understood health impacts of complex toxic cyanobacterial blooms and indicate that currently applied monitoring practices may underestimate actual risks.
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Toxinas Bacterianas/farmacología , Comunicación Celular/efectos de los fármacos , Cylindrospermopsis/metabolismo , Uniones Comunicantes/efectos de los fármacos , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , RatasRESUMEN
Microcystins are cyclic peptide toxins with hepatotoxic and tumour-promoting properties which are produced in high quantities in freshwater cyanobacterial water blooms, and several studies have reported microcystin accumulation in fish with possible food transfer to humans. In this study, we provide the first comparison of liquid chromatography with single mass-spectrometric and with tandem mass-spectrometric detection for analyses of microcystins in complex fish tissue samples. Use of traditional single mass spectrometry (i.e. monitoring of ions with m/z 519.5 for microcystin-RR and m/z 995.5 for microcystin-LR) was found to provide false-positive responses, thus overestimating the concentrations of microcystins in the tissue samples. More selective tandem mass spectrometry seems to provide more reliable results. The concentrations of microcystins detected by tandem mass spectrometry in fish from controlled-exposure experiments were more than 50% lower in comparison with concentrations obtained by single mass spectrometry. Extensive analyses of edible fish parts-muscles (148 fish specimens from eight different species from five natural reservoirs with dense cyanobacterial water blooms)-showed negligible microcystin concentrations (all analyses below the limit of detection; limit of detection of 1.2-5.4 ng/g fresh weight for microcystin-RR, microcystin-YR and microcystin-LR in multiple reaction monitoring mode). Our findings have practical consequences for critical re-evaluation of the health risks of microcystins accumulated in fish.
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Cromatografía Liquida/métodos , Peces , Espectrometría de Masas/métodos , Microcistinas/análisis , AnimalesRESUMEN
Organic pollution is a complex mixture where besides usually discussed polycyclic aromatic hydrocarbons (PAHs) a lot of other toxic or potentially toxic compounds occur. In this case, the organic air pollution in two important industrial cities, Sarajevo and Tuzla, in Bosnia and Herzegovina (part of former Yugoslavia) was assessed with the emphasis placed on genotoxic risks using both chemical (PAHs analyses) and biological approaches (genotoxicity testing with a screening bacterial genotoxicity test - SOS chromotest). The study was performed as a part of the APOPSBAL project (ICA2-CT2002-10007). So far there has not been any information either about the PAHs pollution or the genotoxic activity of the organic air pollution for the localities under the study. Therefore, the presented information is considered absolutely unique. Both used approaches made possible to identify the localities with the highest pollution level and genotoxic risks in both cities. Generally, higher levels of both parameters were determined in Tuzla, which is much more industrialized than Sarajevo, and especially at localities close to city centers and affected by traffic emissions, but also at localities polluted by emissions from industry and household heating. Even if benzo(a)pyrene concentrations exceeded the maximum permitted levels for this pollutant at some localities in Tuzla, the PAHs concentrations were fully comparable with the levels determined in other industrial European cities. Significant genotoxicity of the organic extracts was detected for almost all of the urban localities in the test both without (-S9; direct genotoxicity) and with the addition of metabolic activation (+S9; indirect genotoxicity). The observed direct genotoxic activities were discussed in relation to a potential presence of PAHs derivatives in the air. The indirect genotoxic activities were apparently higher at the localities with higher contents of carcinogenic PAHs. The significant relationship between the determined genotoxic activities and the PAHs pollution was also confirmed by a regression analysis. However, the correlations were not absolute because the observed genotoxic activity was also dependent on the presence of other organic pollutants than the PAHs. It concerns predominantly direct genotoxicity which is not related with the PAHs, but with their nitro-, oxi-, and hydroxy-derivatives and also other unknown polar organic pollutants. However, the concentrations of the direct genotoxins apparently correlated with the PAHs contents in the air. The study showed that screening genotoxicity tests, such as the SOS chromotest, could be effectively used for the identification of localities with increased genotoxic risks. In comparison with the health risk assessment which is usually based on the chemical analyses of only a small part of the pollution mixture, the bioassays enable us to evaluate the risks of all the mixture. The localities with the highest detected human health risks according to the screening bioassays may then be analyzed in detail with specific chemical methods to identify their causes.
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Contaminación del Aire/análisis , Monitoreo del Ambiente , Benzo(a)pireno/análisis , Bosnia y Herzegovina , Ciudades , Pruebas de Mutagenicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Análisis de Regresión , Medición de RiesgoRESUMEN
In this study, organic extracts of total suspended particles (TSP) and the particulate matter (PM) with the size below 2.5 microm (PM(2.5)) combined with organic extracts of the gas phase (GP) collected at two urban and two background localities were analyzed with a bacterial genotoxicity test, SOS chromotest, and an in vitro test for the dioxin toxicity determination, using a modified cell-line of rat hepatoma H4IIE.luc. In addition, the samples of TSP and GP were analyzed for PAHs contents. The PAHs concentrations and both of the toxic activities at the urban localities were much higher than ones at the background localities. Predominantly, traffic was a source of the urban air pollution there which was also confirmed by the evaluation of portions of certain PAHs (BaP/BPE, PYR/BaP) at the localities. On the other hand, the background localities were apparently affected by a long-distance transport of the pollutants from urban and industrial centers. The results of the bioassays indicated potential health risks for the population exposed to the organic air pollutants, especially at the urban localities. Based on the collected samples, distribution of the organic pollutants with the toxic effects in the air was evaluated. The significant portion of the direct genotoxins was bound to the particles larger than 2.5 microm. On the contrary, the indirect genotoxins were bound predominantly to the particles with the size below 2.5 microm. However, in the urban air they may be also bound to the larger particles, as well. While the direct genotoxicity may be related with the presence of PAH-derivatives as well as some polar organic pollutants, the indirect genotoxicity is related with the detected carcinogenic PAHs. But besides the above specified pollutants it is also necessary to consider the presence of other toxic components of the complex organic air pollution mixture that may also show potential health risks. This study demonstrates application of the combination of the screening bioassays for the evaluation of organic air pollution and identification of its health risks.
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Contaminantes Atmosféricos/toxicidad , Contaminación del Aire , Monitoreo del Ambiente/métodos , Mutágenos/toxicidad , Compuestos Orgánicos/toxicidad , Contaminantes Atmosféricos/análisis , Animales , Bioensayo , Línea Celular Tumoral , Pruebas de Mutagenicidad , Mutágenos/análisis , Compuestos Orgánicos/análisis , Material Particulado/análisis , Material Particulado/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/toxicidad , RatasRESUMEN
Innate and adaptive immunity are connected via antigen processing and presentation (APP), which results in the presentation of antigenic peptides to T cells in the complex with the major histocompatibility (MHC) determinants. MHC class II (MHC II) determinants present antigens to CD4+ T cells, which are the main regulators of the immune response. Their genes are transcribed from compact promoters that form first the MHC II enhanceosome, which contains DNA-bound activators and then the MHC II transcriptosome with the addition of the class II transactivator (CIITA). CIITA is the master regulator of MHC II transcription. It is expressed constitutively in dendritic cells (DC) and mature B cells and is inducible in most other cell types. Three isoforms of CIITA exist, depending on cell type and inducing signals. CIITA is regulated at the levels of transcription and post-translational modifications, which are still not very clear. Inappropriate immune responses are found in several diseases, including cancer and autoimmunity. Since CIITA regulates the expression of MHC II genes, it is involved directly in the regulation of the immune response. The knowledge of CIITA will facilitate the manipulation of the immune response and might contribute to the treatment of these diseases.
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Genes MHC Clase II , Antígenos de Histocompatibilidad Clase II/metabolismo , Linfocitos B/inmunología , Regulación de la Expresión Génica , Antígenos de Histocompatibilidad Clase II/genética , Humanos , Inmunidad Innata , Proteínas Nucleares/química , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Linfocitos T/inmunología , Transactivadores/química , Transactivadores/genética , Transactivadores/metabolismoRESUMEN
Various molecular interactions not operating in other cell types are most likely required for mammalian oocytes to develop into fully competent eggs. This study seeks to initiate analyses of the potential oocyte-specific functions of regulators of G1/S progression-CDK4, CDK6, D-type cyclins, and p27-by first determining their expression patterns in growing and maturing mouse oocytes and in mouse embryos early after fertilization. Western blot and immunofluorescence analyses on isolated oocytes were employed to evaluate both their levels and their localization. The data show that 1). mouse oocytes contain significant amounts of all studied regulators; 2). their amounts and localization undergo dramatic changes as the oocytes grow, meiotically mature, and transit into embryogenesis; and 3). some regulators (CDK4, CDK6, cyclin D2, and p27) appear in unusual, most likely posttranslationally modified, forms. These data distinguish G1/S regulators as the potential players in molecular processes that are important for oocytes to function normally.
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Proteínas de Ciclo Celular/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/metabolismo , Oocitos/metabolismo , Proteínas Proto-Oncogénicas , Proteínas Supresoras de Tumor/metabolismo , Animales , Western Blotting , División Celular/fisiología , Ciclina D , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Femenino , Fase G1/fisiología , Meiosis/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Oocitos/citología , Embarazo , Fase S/fisiologíaRESUMEN
A comparison of the modelling results of persistent, bioaccumulative and toxic (PBT) chemicals is presented with measurements. Contribution will present mean annual concentrations calculated and observed at EMEP stations and their ratios. The comparison of the calculated results with older results indicates that the model modification improved the agreement with measurement data. PBT compounds in ambient air are monitored in the area of Kosetice observatory (professional observatory of the Czech Hydrometeorological Institute located in south Bohemia). Calculated and measured mean annual concentrations of PBTs in precipitation, soil, vegetation and their ratios are presented. It should be mentioned that the number of measurements in such compartments as seawater, soil and vegetation is insufficient for model verification at present. The agreement between results from MSC-East models and results from long-term regional air background monitoring in Central Europe is good.
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Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Modelos Teóricos , Compuestos Orgánicos/análisis , Contaminantes del Suelo/análisis , Plantas/química , Movimientos del AguaRESUMEN
This review describes problems with persistent and bioaccumulative organic substances which posses toxic characteristics likely to cause adverse human health or environmental effects in countries of Central and Eastern Europe as far as human exposure is concerned. This paper is a part of a more detailed report on the subject.
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Monitoreo del Ambiente , Contaminantes Ambientales/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Europa Oriental , Contaminación de Alimentos , Humanos , Leche Humana/químicaRESUMEN
The sources and environmental levels of the PBTs in the countries of Central and Eastern Europe are broadly described. Most of the countries in the region produce and/or formulate pesticides. The pesticide registration is a primary requirement for import, production and distribution. The special attention must be given to unwanted pesticides. The problem of unwanted and expired pesticides pose the greatest danger to the natural environment and people which is brought about by the use of chemicals in agriculture in CEE countries. Countries still have not solve the problem of safety storage for PBTs and other chemicals classified as poisons and they have no special sites or facilities for destruction of these chemicals. This region has very specific problems of environmental pollution, which are the results of the recent wars. Destruction of industrial facilities and spilling of chemicals have the worst effect for the environment (Bosnia and Herzegovina, Croatia, Serbia and Montenegro).
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Contaminantes Ambientales/análisis , Residuos de Plaguicidas/análisis , Europa Oriental , Insecticidas/análisis , Bifenilos Policlorados/análisisRESUMEN
Ubiquitination is a universal protein degradation pathway in which the molecules of 8.5-kDa proteolytic peptide ubiquitin are covalently attached to the epsilon-amino group of the substrate's lysine residues. Little is known about the importance of this highly conserved mechanism for protein recycling in mammalian gametogenesis and fertilization. The data obtained by the students and faculty of the international training course Window to the Zygote 2000 demonstrate the accumulation of ubiquitin-cross-reactive structures in the trophoblast, but not in the inner cell mass of the expanding bovine and mouse blastocysts. This observation suggests that a major burst of ubiquitin-dependent proteolysis occurs in the trophoblast of mammalian peri-implantation embryos. This event may be important for the success of blastocyst hatching, differentiation of embryonic stem cells into soma and germ line, and/or implantation in both naturally conceived and reconstructed mammalian embryos.
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Mamíferos/embriología , Trofoblastos/metabolismo , Ubiquitina/metabolismo , Animales , Biomarcadores/análisis , Blastocisto/metabolismo , Bovinos , Células Cultivadas , Ratones , Ratones Endogámicos ICRRESUMEN
The v-myb oncogene of avian myeloblastosis virus causes acute monoblastic leukemia in vivo and transforms myelomonocytic cells in culture. Retinoids are potent regulators of proliferation and differentiation in various cell types, and they can initiate differentiation in certain types of leukemic cells. However, the BM2 v-myb-transformed chicken monoblastic cell line is resistant to retinoic acid treatment. We found that overexpression of the retinoid X receptor confers sensitivity of BM2 cells to retinoic acid, resulting in induction of growth arrest and terminal differentiation. In contrast, the frequency of apoptosis was not affected by the retinoid X receptor in this cell type. We also demonstrated that suppression of transformation by v-Myb results from the negative effect of retinoid X receptor on v-Myb transactivation function, similar to that previously described for the retinoic acid receptor. The retinoid X receptor-induced inhibition of transactivation by v-Myb seems to be enhanced by a cell type-specific factor(s), which is not required by retinoic acid receptor.