Myc | EPFL Graph Search

Myc (c-myc) est un protooncogène qui est surexprimé dans certains cancers humains. Quand il est soumis à des mutations ou à une surexpression, il stimule la prolifération des cellules et se conduit comme un oncogène. Le gène MYC produit un facteur de transcription qui régule l'expression de 15 % de tous les gènes en se liant aux séquences Enhancer Box (les E-boxes) et en recrutant des enzymes capables d'acétyler les acides aminés lysine des histone (histone acetyltransferase). Myc appartient à la famille des facteurs de transcription myc, qui inclut aussi les gènes n-myc et l-myc. Découverte Le gène MYC est découvert pour la première fois chez des patients atteints du lymphome de Burkitt. Dans cette maladie, des cellules cancéreuses sont sujettes à des translocations de chromosomes, en particulier sur le chromosome 8 humain. En clonant les points de cassure des chromosomes fusionnés, il a été mis en évidence un gène qui était similaire à un oncogène véhiculé par le virus a

The role of Myc in bone metabolism

Raphaëlle Stuer

Various studies have proven the involvement of Myc in cell growth and proliferation but also cell transformation and tumorigenesis. Since regulation of cell proliferation and differentiation is mandatory in bone metabolism, we investigated the role of Myc in osteoblasts. Studies involving osteoblast specific deletion of c-Myc traced by EYFP revealed no difference in fluorescence comparing mice that have either two copies, one copy or that are lacking both copies of c-Myc under the microscope. FACS analysis of these same mice showed no significant difference in numbers of EYFP positive osteoblasts among these mice. Immunofluorescence stainings showed absence of c-Myc protein in the majority of EYFP positive cells. Studies involving osteoblast specific c-Myc and N-Myc deletion traced by EYFP were performed to analyze possible consequences of loss of both genes. Bones of newborn myc-deficient mice appeared EYFP fluorescent under the microscope. FACS analysis of myc-deficient mice demonstrated variable numbers of EYFP positive osteoblasts. However, numbers of EYFP positive osteoblasts were in the same range as numbers obtained by FACS for c-Myc deficient mice. Osteoblast specific overexpression of c-Myc was analyzed using a Tet-Off model in which human c-Myc is overexpressed. qRT-PCRs showed that markers of mid to late differentiation of osteoblasts are less expressed in mice overexpressing c-Myc compared to control mice. Since mutant mice develop osteosarcomas, the expression levels of osteoblast differentiation markers were tested by qRT-PCR. Tumors revealed to be composed of overall less differentiated osteoblasts. Using these two models we could show that myc is dispensable for osteoblasts in vivo, whereas ectopic expression of c-myc leads to severe changes in the transcription profile of osteoblasts with a specific loss of mature osteoblast markers, and to the development of osteosarcomas, which show a rather immature osteoblast phenotype

2009

Placental rescue reveals a sole requirement for c-Myc in embryonic erythroblast survival and hematopoietic stem cell function

Armin Ehninger

The c-Myc protein has been implicated in playing a pivotal role in regulating the expression of a large number of genes involved in many aspects of cellular function. Consistent with this view, embryos lacking the c-myc gene exhibit severe developmental defects and die before midgestation. Here, we show that Sox2Cre-mediated deletion of the conditional c-myc(flox) allele specifically in the epiblast (hence trophoectoderm and primitive endoderm structures are wild type) rescues the majority of developmental abnormalities previously characterized in c-myc knockout embryos, indicating that they are secondary defects and arise as a result of placental insufficiency. Epiblast-restricted c-Myc-null embryos appear morphologically normal and do not exhibit any obvious proliferation defects. Nonetheless, these embryos are severely anemic and die before E12. c-Myc-deficient embryos exhibit fetal liver hypoplasia, apoptosis of erythrocyte precursors and functionally defective definitive hematopoietic stem/progenitor cells. Specific deletion of c-myc(flox) in hemogenic or hepatocytic lineages validate the hematopoietic-specific requirement of c-Myc in the embryo proper and provide in vivo evidence to support a synergism between hematopoietic and liver development. Our results reveal for the first time that physiological levels of c-Myc are essential for cell survival and demonstrate that, in contrast to most other embryonic lineages, erythroblasts and hematopoietic stem/progenitor cells are particularly dependent on c-Myc function.

2008

Selective Requirement for c-Myc at an Early Stage of V alpha 14i NKT Cell Development

Wei Jiang, Anne Wilson

V alpha 14 invariant (V alpha 14i) NKT cells are a subset of regulatory T cells that utilize a semi-invariant TCR to recognize glycolipids associated with monomorphic CD1d molecules. During development in the thymus, CD4(+)CD8(+) V alpha 14i NKT precursors recognizing endogenous CD1d-associated glycolipids on other CD4(+)CD8(+) thymocytes are selected to undergo a maturation program involving sequential expression of CD44 and NK-related markers such as NK1.1. The molecular requirements for V alpha 14i NKT cell maturation, particularly at early developmental stages, remain poorly understood. In this study, we show that CD4-Cre-mediated T cell-specific inactivation of c-Myc, a broadly expressed transcription factor with a wide range of biological activities, selectively impairs V alpha 14i NKT cell development without perturbing the development of conventional T cells. In the absence of c-Myc, V alpha 14i NKT cell precursors are blocked at an immature CD44(low)NK1.1(-) stage in a cell autonomous fashion. Residual c-Myc-deficient immature V alpha 14i NKT cells appear to proliferate normally, cannot be rescued by transgenic expression of BCL-2, and exhibit characteristic features of immature V alpha 14i NKT cells such as high levels of preformed IL-4 mRNA and the transcription factor promyelocytic leukemia zinc finger. Collectively our data identify c-Myc as a critical transcription factor that selectively acts early in V alpha 14i NKT cell development to promote progression beyond the CD44(low)NK1.1(-) precursor stage. The Journal of Immunology, 2009, 182: 4641-4648.

2009

The role of Myc in bone metabolism

Raphaëlle Stuer

2009