Publikationen


Suche nach „[C.] [Hellerbrand]“ hat 2 Publikationen gefunden
Suchergebnis als PDF
    GesundAngewandte Gesundheitswissenschaften

    Zeitschriftenartikel

    Melanie Kappelmann-Fenzl, S. Kuphal, R. Krupar, D. Schadendorf, V. Umansky, L. Vardimon, C. Hellerbrand, A. Bosserhoff

    Complex Formation with Monomeric α-Tubulin and Importin 13 Fosters c-Jun Protein Stability and Is Required for c-Jun's Nuclear Translocation and Activity

    Cancers, vol. 11, no. 11, pp. 1-12

    2019

    DOI: 10.3390/cancers11111806

    Abstract anzeigen

    Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers. They are essential for a number of cellular processes, including intracellular trafficking and mitosis. Tubulin-binding chemotherapeutics are used to treat different types of tumors, including malignant melanoma. The transcription factor c-Jun is a central driver of melanoma development and progression. Here, we identify the microtubule network as a main regulator of c-Jun activity. Monomeric α-tubulin fosters c-Jun protein stability by protein-protein interaction. In addition, this complex formation is necessary for c-Jun's nuclear localization sequence binding to importin 13, and consequent nuclear import and activity of c-Jun. A reduction in monomeric α-tubulin levels by treatment with the chemotherapeutic paclitaxel resulted in a decline in the nuclear accumulation of c-Jun in melanoma cells in an experimental murine model and in patients' tissues. These findings add important knowledge to the mechanism of the action of microtubule-targeting drugs and indicate the newly discovered regulation of c-Jun by the microtubule cytoskeleton as a novel therapeutic target for melanoma and potentially also other types of cancer.

    GesundAngewandte Gesundheitswissenschaften

    Zeitschriftenartikel

    L. Feuerer, S. Lamm, I. Henz, Melanie Kappelmann-Fenzl, S. Haferkamp, S. Meierjohann, C. Hellerbrand, S. Kuphal, A. Bosserhoff

    Role of MIA (melanoma inhibitory activity) in melanocyte senescence

    Pigment Cell & Melanoma Research, no. First Published: 06 June 2019

    2019

    DOI: 10.1111/pcmr.12801

    Abstract anzeigen

    The protein MIA is known to be expressed in melanoma and to support melanoma progression. Interestingly, previous studies also observed the expression of MIA in nevi. Concentrating on these findings, we revealed that MIA expression is correlated with a senescent state in melanocytes. Induction of replicative or oncogene‐induced senescence resulted in increased MIA expression in vitro. Notably, MIA‐knockdown in senescent melanocytes reduced the percentage of senescence‐associated beta‐Gal‐positive cells and enhanced proliferation. Using the melanoma mouse model Tg(Grm1), MIA‐deficient mice supported the impact of MIA on senescence by showing a significantly earlier tumor onset compared to controls. In melanocytes, MIA‐knockdown led to a downregulation of the cell cycle inhibitor p21 in vitro and in vivo. In contrast, after induction of hTERT in human melanoma cells, p21 regulation by MIA was lost. In summary, our data show for the first time that MIA is a regulator of cellular senescence in human and murine melanocytes.