News from the Institute

RAF kinases are direct RAS effector proteins and upon activation they trigger the classical MAPK signaling pathway that control various fundamental cellular processes. RAF family comprises of ARAF, BRAF and CRAF of which ARAF remains understudied. In a cover story published this week in Science Signaling, Krishna Rajalingam's group demonstrate an obligatory role for ARAF kinase in mediating MEK1/2-ERK1/2 activation and tumour cell migration in a cell type dependent manner.

Krishnaraj Rajalingam, a group leader from IBCII and a BIF-PLUS3 fellow got selected for the prestigious W3 Heisenberg professorship in Cell Biology from the DFG. With this award he joins the Forschungszentrum für Immuntherapie (FZI) at the Johannes Gutenberg-Universität Mainz (JGU) to establish a cell biology unit. IBCII director Prof. Ivan Dikic congratulates Krishna on this accomplishment!

Mitogen activated protein kinases (MAPKs) are a class of highly conserved family of protein kinases that control fundamental cellular processes like cell survival, migration and differentiation. The group of Krishna Rajalingam from IBCII, now discovers a novel role for ubiquitination in the inactivation of MEKK2/3-MEK5-ERK5 signaling pathway, thus adding another layer of regulation of MAPKs. They identify that two members of the inhibitors of Apoptosis Proteins (IAPs) family, XIAP and cIAP1, directly bind and conjugate a unique type of ubiquitin chains to MEKK2 and MEKK3, which directly impairs the complex formation between MEK5 and ERK5 thus inactivating this signalling pathway. They further identify that XIAP negatively controls human myogenic differentiation by regulating the activation dynamics of ERK5-MAPK cascade. The observations by Takeda AN et al are now published in EMBOJ

The group of Stefan Müller unraveled a novel facet of SUMO-regulated gene expression. They discovered that the SUMO-specific isopeptidase SENP3 is needed for proper activity of histone-modifying MLL1/2 complexes. Removal of SUMO2/3 from the MLL1/2 subunit RbBP5 is required for the activation of a subset of HOX genes, including the regulator of osteogenic differentiation DLX3. The importance of this pathway for cell differentiation was demonstrated in a human stem cell model.  The paper by Nayak et al. was published online in Molecular Cell on June, 12.

The International Human Frontier Science Program (HFSP) Organization announced this year's winners of the competition for one of the prestigious HFSP research grants. Amongst the awardees is the Dikic group, who together with the Sidhu group (Canada), the Komatsu group (Japan) and the Sander group (U.S.) will receive 1,35 M USD for the next 3 years. "This award considerably pushes autophagy research in Frankfurt, especially because it funds one of our most innovative projects. Within the next 3 years, we expect to gain a lot of knowledge about molecular targeting of the autophagy network", says Ivan Dikic, IBCII director.