Myb proteins inhibit fibroblast transformation by v-Rel

Genes that cause cancer have been divided into two general classes – oncogenes that act in a dominant fashion to transform normal cells into a malignant state, and tumor suppressor genes that act in a dominant fashion to prevent such transformation. In this report, we demonstrate that both the v-myb retroviral oncogene, which causes leukemic transformation of hematopoietic cells, and the c-myb proto-oncogene can also function as inhibitors of fibroblast transformation by the v-rel oncogene. These results imply that the myb genes can function either as oncogenes or as tumor suppressors in different cellular contexts

Transcriptional activation by the Myb proteins requires a specific local promoter structure

AbstractThe 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) PyAACT/GG 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

A conserved acidic patch in the Myb domain is required for activation of an endogenous target gene and for chromatin binding

The c-Myb protein is a transcriptional regulator initially identified by homology to the v-Myb oncoprotein, and has since been implicated in human cancer. The most highly conserved portion of the c-Myb protein is the DNA-binding domain which consists of three imperfect repeats. Many other proteins contain one or more Myb-related domains, including a number of proteins that do not bind directly to DNA. We performed a phylogenetic analysis of diverse classes of Myb-related domains and discovered a highly conserved patch of acidic residues common to all Myb-related domains. These acidic residues are positioned in the first of three alpha-helices within each of the three repeats that comprise the c-Myb DNA-binding domain. Interestingly, these conserved acidic residues are present on a surface of the protein which is distinct from that which binds to DNA. Alanine mutagenesis revealed that the acidic patch of the third c-Myb repeat is essential for transcriptional activity, but neither for nuclear localization nor DNA-binding. Instead, these acidic residues are required for efficient chromatin binding and interaction with the histone H4 N-terminal tail

Structural mechanism of Myb-MuvB assembly.

The MuvB transcriptional regulatory complex, which controls cell-cycle-dependent gene expression, cooperates with B-Myb to activate genes required for the G2 and M phases of the cell cycle. We have identified the domain in B-Myb that is essential for the assembly of the Myb-MuvB (MMB) complex. We determined a crystal structure that reveals how this B-Myb domain binds MuvB through the adaptor protein LIN52 and the scaffold protein LIN9. The structure and biochemical analysis provide an understanding of how oncogenic B-Myb is recruited to regulate genes required for cell-cycle progression, and the MMB interface presents a potential therapeutic target to inhibit cancer cell proliferation

Pengembangan Modul Intervensi Untuk Meningkatkan Resiliensi Pada Individu Yang Mengalami Perubahan Fisik Menjadi Penyandang Disabilitas

Penelitian ini bertujuan untuk menindaklanjuti temuan sebelumnya dengan mengembangkan modul intervensi secara terperinci, yang selanjutnya dapat digunakan sebagai panduan dalam membantu meningkatkan resiliensi individu yang mengalami Perubahan kondisi fisik menjadi penyandang disabilitas. Penulis menyusun serta merinci rancangan implementasi awal yang direkomendasikan oleh penelitian sebelumnya kedalam langkah-langkah yang lebih sistematis dan operasional hingga memperoleh hasil akhir berupa modul. Metode yang digunakan berbasis tahapan riset aksi, meskipun proses yang dilakukan hanya sampai pada langkah ketiga, yaitu Perumusan solusi dari persoalan yang diangkat. Partisipan terdiri dari delapan individu yang mengalami Perubahan kondisi menjadi penyandang disabilitas. Selain partisipan, empat orang psikolog juga dilibatkan dalam penelitian ini sebagai penelaah modul. Hasil penelitian ini berupa sebuah paket modul intervensi untuk peningkatan resiliensi melalui penguatan faktor protektif serta pengembangan strategi koping dan adaptasi pada individu yang mengalami Perubahan kondisi fisik menjadi penyandang disabilitas. Paket modul tersebut terdiri dari 5 sub-modul yang telah disusun sedemikian rupa untuk memudahkan pelaksanaannya, terdiri dari modul: (1) memperkuat dukungan keluarga terhadap penyandang disabilitas; (2) pendampingan awal penyandang disabilitas; (3) intervensi lanjut 1 (penguatan faktor protektif internal); (4) intervensi lanjut 2 (pengembangan strategi koping); dan (5) intervensi lanjut 3 (langkah adaptasi positif)

A Putative Transcription Factor MYT1 Is Required for Female Fertility in the Ascomycete Gibberella zeae

Gibberella zeae is an important pathogen of major cereal crops. The fungus produces ascospores that forcibly discharge from mature fruiting bodies, which serve as the primary inocula for disease epidemics. In this study, we characterized an insertional mutant Z39P105 with a defect in sexual development and identified a gene encoding a putative transcription factor designated as MYT1. This gene contains a Myb DNA-binding domain and is conserved in the subphylum Pezizomycotina of Ascomycota. The MYT1 protein fused with green fluorescence protein localized in nuclei, which supports its role as a transcriptional regulator. The MYT1 deletion mutant showed similar phenotypes to the wild-type strain in vegetative growth, conidia production and germination, virulence, and mycotoxin production, but had defect in female fertility. A mutant overexpressing MYT1 showed earlier germination, faster mycelia growth, and reduced mycotoxin production compared to the wild-type strain, suggesting that improper MYT1 expression affects the expression of genes involved in the cell cycle and secondary metabolite production. This study is the first to characterize a transcription factor containing a Myb DNA-binding domain that is specific to sexual development in G. zeae

Quantitative trait loci mapping reveals candidate pathways regulating cell cycle duration in Plasmodium falciparum

<p>Abstract</p> <p>Background</p> <p>Elevated parasite biomass in the human red blood cells can lead to increased malaria morbidity. The genes and mechanisms regulating growth and development of <it>Plasmodium </it><it>falciparum </it>through its erythrocytic cycle are not well understood. We previously showed that strains HB3 and Dd2 diverge in their proliferation rates, and here use quantitative trait loci mapping in 34 progeny from a cross between these parent clones along with integrative bioinformatics to identify genetic loci and candidate genes that control divergences in cell cycle duration.</p> <p>Results</p> <p>Genetic mapping of cell cycle duration revealed a four-locus genetic model, including a major genetic effect on chromosome 12, which accounts for 75% of the inherited phenotype variation. These QTL span 165 genes, the majority of which have no predicted function based on homology. We present a method to systematically prioritize candidate genes using the extensive sequence and transcriptional information available for the parent lines. Putative functions were assigned to the prioritized genes based on protein interaction networks and expression eQTL from our earlier study. DNA metabolism or antigenic variation functional categories were enriched among our prioritized candidate genes. Genes were then analyzed to determine if they interact with cyclins or other proteins known to be involved in the regulation of cell cycle.</p> <p>Conclusions</p> <p>We show that the divergent proliferation rate between a drug resistant and drug sensitive parent clone is under genetic regulation and is segregating as a complex trait in 34 progeny. We map a major locus along with additional secondary effects, and use the wealth of genome data to identify key candidate genes. Of particular interest are a nucleosome assembly protein (PFL0185c), a Zinc finger transcription factor (PFL0465c) both on chromosome 12 and a ribosomal protein L7Ae-related on chromosome 4 (PFD0960c).</p

A Putative Transcription Factor MYT2 Regulates Perithecium Size in the Ascomycete Gibberella zeae

The homothallic ascomycete fungus Gibberella zeae is a plant pathogen that is found worldwide, causing Fusarium head blight (FHB) in cereal crops and ear rot of maize. Ascospores formed in fruiting bodies (i.e., perithecia) are hypothesized to be the primary inocula for FHB disease. Perithecium development is a complex cellular differentiation process controlled by many developmentally regulated genes. In this study, we selected a previously reported putative transcription factor containing the Myb DNA-binding domain MYT2 for an in-depth study on sexual development. The deletion of MYT2 resulted in a larger perithecium, while its overexpression resulted in a smaller perithecium when compared to the wild-type strain. These data suggest that MYT2 regulates perithecium size differentiation. MYT2 overexpression affected pleiotropic phenotypes including vegetative growth, conidia production, virulence, and mycotoxin production. Nuclear localization of the MYT2 protein supports its role as a transcriptional regulator. Transcriptional analyses of trichothecene synthetic genes suggest that MYT2 additionally functions as a suppressor for trichothecene production. This is the first study characterizing a transcription factor required for perithecium size differentiation in G. zeae, and it provides a novel angle for understanding sexual development in filamentous fungi

Genome-Wide Identification of R2R3-MYB Genes and Expression Analyses During Abiotic Stress in

The R2R3-MYB is one of the largest families of transcription factors, which have been implicated in multiple biological processes. There is great diversity in the number of R2R3-MYB genes in different plants. However, there is no report on genome-wide characterization of this gene family in cotton. In the present study, a total of 205 putative R2R3-MYB genes were identified in cotton D genome (Gossypium raimondii), that are much larger than that found in other cash crops with fully sequenced genomes. These GrMYBs were classified into 13 groups with the R2R3-MYB genes from Arabidopsis and rice. The amino acid motifs and phylogenetic tree were predicted and analyzed. The sequences of GrMYBs were distributed across 13 chromosomes at various densities. The results showed that the expansion of the G. Raimondii R2R3-MYB family was mainly attributable to whole genome duplication and segmental duplication. Moreover, the expression pattern of 52 selected GrMYBs and 46 GaMYBs were tested in roots and leaves under different abiotic stress conditions. The results revealed that the MYB genes in cotton were differentially expressed under salt and drought stress treatment. Our results will be useful for determining the precise role of the MYB genes during stress responses with crop improvement