Université de Fribourg

The atypical kinase RIOK1 promotes tumor growth and invasive behavior

Weinberg, Florian ; Reischmann, Nadine ; Fauth, Lisa ; Taromi, Sanaz ; Mastroianni, Justin ; Köhler, Martin ; Halbach, Sebastian ; Becker, Andrea C. ; Deng, Niantao ; Schmitz, Tatjana ; Uhl, Franziska Maria ; Herbener, Nicola ; Riedel, Bianca ; Beier, Fabian ; Swarbrick, Alexander ; Lassmann, Silke ; Dengjel, Jörn ; Zeiser, Robert ; Brummer, Tilman

In: EBioMedicine, 2017, vol. 20, p. 79–97

Despite being overexpressed in different tumor entities, RIO kinases are hardly characterized in mammalian cells. We investigated the role of these atypical kinases in different cancer cells. Using isogenic colon-, breast- and lung cancer cell lines, we demonstrate that knockdown of RIOK1, but not of RIOK2 or RIOK3, strongly impairs proliferation and invasiveness in conventional and 3D...

Université de Fribourg

Discrete cytosolic macromolecular BRAF complexes exhibit distinct activities and composition

Diedrich, Britta ; Rigbolt, Kristoffer TG ; Röring, Michael ; Herr, Ricarda ; Kaeser‐Pebernard, Stephanie ; Gretzmeier, Christine ; Murphy, Robert F ; Brummer, Tilman ; Dengjel, Jörn

In: The EMBO Journal, 2017, vol. 36, no. 5, p. 646–663

As a central element within the RAS/ERK pathway, the serine/threonine kinase BRAF plays a key role in development and homeostasis and represents the most frequently mutated kinase in tumors. Consequently, it has emerged as an important therapeutic target in various malignancies. Nevertheless, the BRAF activation cycle still raises many mechanistic questions as illustrated by the paradoxical...

Université de Fribourg

Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles

Eisenhardt, Anja E. ; Sprenger, Adrian ; Röring, Michael ; Herr, Ricarda ; Weinberg, Florian ; Köhler, Martin ; Braun, Sandra ; Orth, Joachim ; Diedrich, Britta ; Lanner, Ulrike ; Tscherwinski, Natalja ; Schuster, Simon ; Dumaz, Nicolas ; Schmidt, Enrico ; Baumeister, Ralf ; Schlosser, Andreas ; Dengjel, Jörn ; Brummer, Tilman

In: Oncotarget, 2016, vol. 7, no. 18, p. 26628–26652

B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK-pathway and a pharmacological target of growing clinical relevance, in particular in oncology. To understand how B-Raf itself is regulated, we combined mass spectrometry with genetic approaches to map its interactome in MCF-10A cells as well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1...