Jeannette Gogel

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Resistance towards the proteasome inhibitor bortezomib is poorly understood. We adapted the HL-60, ARH-77 and AMO-1 cell lines (myeloid leukemia, plasmocytoid lymphoma, myeloma) to bortezomib exceeding therapeutic plasma levels, and compared characteristics of the ubiquitin–proteasome system, alternative proteases and the unfolded protein response (UPR)(More)
OBJECTIVES I(Ks), the slow component of the delayed rectifier potassium current, underlies a strong beta-adrenergic regulation in the heart. Catecholamines, like isoproterenol, induce a strong increase in I(Ks). Recent work has pointed to an opposing biological effect of beta(1)- and beta(3)-adrenoceptors in the heart. However the role of these subtypes in(More)
Proteasomal proteolysis relies on the activity of six catalytically active proteasomal subunits (β1, β2, β5, β1i, β2i and β5i). Applying a functional proteomics approach, we used a recently developed activity-based, cell-permeable proteasome-specific probe that for the first time allows differential visualization of individual active proteasomal subunits in(More)
In melanoma, the PI3K-AKT-mTOR (AKT) and RAF-MEK-ERK (MAPK) signaling pathways are constitutively activated and appear to play a role in chemoresistance. Herein, we investigated the effects of pharmacological AKT and MAPK pathway inhibitors on chemosensitivity of melanoma cells to cisplatin and temozolomide. Chemosensitivity was tested by examining effects(More)
The biosynthesis of immunoglobulin leads to constitutive endoplasmic reticulum (ER) stress in myeloma cells, which activates the unfolded protein response (UPR). The UPR promotes protein folding by chaperones and increases proteasomal degradation of misfolded protein. Excessive ER stress induces apoptosis and represents a molecular basis for the bortezomib(More)
Plaque-type blue nevus is a rare variant of blue nevus characterized by grouped nodules displaying histomorphological features of a cellular blue nevus. We report the clinical, histopathologic and immunohistologic features of a patient with recurrent nodules in a periauricular plaque-type blue nevus with malignant transformation and fatal outcome. The nevus(More)
Cathepsin E (CatE) and D (CatD) are the major aspartic proteinases in the endolysosomal pathway. They have similar specificity and therefore it is difficult to distinguish between them, as known substrates are not exclusively specific for one or the other. In this paper we present a substrate-based assay, which is highly relevant for immunological(More)
Farnesyl transferase inhibitors (FTIs) inhibit the farnesylation of proteins, including RAS and RHEB (Ras homolog enriched in brain). RAS signals to the RAF-MEK-ERK (MAPK) and PI3K-AKT-mTOR (AKT) signaling pathways, which have a major role in melanoma progression. RHEB positively regulates mammalian target of rapamycin (mTOR). We investigated the effects of(More)
9566 Background: HIV-protease inhibitors like Ritonavir produces regressions in HIV-associated Kaposi's sarcoma, reportedly due to proteasome inhibition. We have here assessed the effect of Ritonavir and the proteasome inhibitor Bortezomib on the viability and proteasome activity of the soft tissue sarcoma cell lines RD (rhabdomyosarcoma) and A-673 (ewing's(More)
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