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  • 1.
    Arabi, Azadeh
    et al.
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institutet.
    Wu, Siqin
    SLU.
    Ridderstråle, Karin
    SLU.
    Bierhoff, Holger
    German Cancer Research Center, Heidelberg, Germany.
    Shiue, Chiounan
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institutet.
    Fatyol, Karoly
    German Cancer Research Center, Heidelberg, Germany.
    Fahlén, Sara
    SLU.
    Hydbring, Per
    SLU.
    Söderberg, Ola
    Uppsala universitet.
    Grummt, Ingrid
    German Cancer Research Center, Heidelberg, Germany.
    Larsson, Lars-Gunnar
    SLU.
    Wright, Anthony P H
    Södertörns högskola, Institutionen för livsvetenskaper. Karolinska Institutet.
    c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription2005Inngår i: Nature Cell Biology, ISSN 1465-7392, E-ISSN 1476-4679, Vol. 7, nr 3, s. 303-310Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The c-Myc oncoprotein regulates transcription of genes that are associated with cell growth, proliferation and apoptosis(1). c-Myc levels are modulated by ubiquitin/proteasome-mediated degradation(1). Proteasome inhibition leads to c-Myc accumulation within nucleoli(2), indicating that c-Myc might have a nucleolar function. Here we show that the proteins c-Myc and Max interact in nucleoli and are associated with ribosomal DNA. This association is increased upon activation of quiescent cells and is followed by recruitment of the Myc cofactor TRRAP, enhanced histone acetylation, recruitment of RNA polymerase I (Pol I), and activation of rDNA transcription. Using small interfering RNAs (siRNAs) against c-Myc and an inhibitor of Myc - Max interactions, we demonstrate that c-Myc is required for activating rDNA transcription in response to mitogenic signals. Furthermore, using the ligand-activated MycER ( ER, oestrogen receptor) system, we show that c-Myc can activate Pol I transcription in the absence of Pol II transcription. These results suggest that c-Myc coordinates the activity of all three nuclear RNA polymerases, and thereby plays a key role in regulating ribosome biogenesis and cell growth.

  • 2. Bakhiet, M
    et al.
    Tjernlund, A
    Mousa, A
    Gad, Annica
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institute.
    Strömblad, Staffan
    Södertörns högskola, Avdelning Naturvetenskap. Karolinska Institute.
    Kuziel, W A
    Seiger, A
    Andersson, J
    RANTES promotes growth and survival of human first-trimester forebrain astrocytes2001Inngår i: Nature Cell Biology, ISSN 1465-7392, E-ISSN 1476-4679, Vol. 3, nr 2, s. 150-157Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have examined the role of alpha and beta chemokines in the promotion of the ontogenetic development of the brain. RANTES was expressed preferentially in human fetal astrocytes in an age-dependent manner. Astrocytes from 5-week-old brains showed high proliferation and reduced survival, whereas 10-week-old astrocytes exhibited opposite effects. These effects were suppressed by anti-RANTES or anti-RANTES receptor antibodies and were enhanced by recombinant RANTES. RANTES induced tyrosine phosphorylation of several cellular proteins and nuclear translocation of STAT-1 in astrocytes. Interferons (IFN-gamma) was required for RANTES effects because RANTES induced IFN-gamma, and only 10-week-old astrocytes expressed the IFN-gamma receptor. Blocking of IFN-gamma with antibody reversed the effects of RANTES, indicating that cytokine/chemokine networks are critically involved in brain development.

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